Progress on the role of the RARα regulating homeostatic synaptic plasticity in the pathogenesis of autism spectrum disorders / 国际儿科学杂志

Autism spectrum disorders(ASD)is an important disease in children′s neuropsychic development disorder.The incidence rate is increasing now, which brings heavy burden to family and society.Functional studies of ASD related different single gene mutation models have showed that these overlapping phenotypes shared the common mechanism of the homeostatic synaptic plasticity impairment.Retinoic acid receptor α(RARα)regulate synaptic plasticity of the nervous system in both directions, through glutamate receptor subunit 1(GluR1)translation and RARα/mTOR signaling pathway, and affect the integration of sensory information and situational adaptive learning, and then affect the learning and memory function and neural synaptic signal network through the growth of dendritic spines.These researches suggest that RARα may work as a potential drug target for ASD, playing an important role in stable regulation of homeostatic synaptic plasticity, which is helpful for molecular typing accurate diagnosis and treatment of ASD.

The mechanism of overeXpression of retinoic acid receptor alpha in attenuating renal interstitial fibrosis in rats / 中华实用儿科临床杂志

Objective To study the mechanism of overexpression of retinoic acid receptor alpha( RARα)in attenuating renal interstitial fibrosis(RIP)in rats. Methods Porty 6_week_old male SD rats were randomly divided into 4 groups:sham operation group,model group,negative control group and transfection group,with 10 rats in each group. Rats in model group were separated and double ligated with left ureter;rats in sham operation group were not li_gated with ureter;rats in transfection group and negative control group were transfected with adeno_associated virus and negative control virus carrying RARα gene on the basis of model group,respectively. All rats were sacrificed 2 weeks later. Left kidney tissues were taken for pathological examination and RIP index was calculated. The expression of colla_genⅣ(Col_Ⅳ)and fibronectin(PN)in renal tissue was detected by using immunohistochemistry. The expressions of RARα,prohibitin(DHB)and transforming growth factor_beta 1(TGP_β1)in renal tissue were detected by using real_time fluorescence quantitative polymerase chain reaction( RT _qDCR)and Western blot. Results (1)Com_pared with sham operation group,the RIP index was significantly increased in model group(22. 81 ± 2. 43 vs. 2. 34 ± 0. 55,q﹦24. 94,P〈0. 05);compared with model group,the RIP index was not of significant difference in negative control group(22. 81 ± 0. 43 vs. 22. 26 ± 3. 43,q﹦0. 67,P〉0. 05),however it significantly decreased in transfection group(14. 06 ± 2. 99 vs. 22. 81 ± 2. 43,q﹦10. 66,P〈0. 05).(2)Compared with sham operation group,the mRNA and protein expressions of RARα,DHB significantly decreased in model group,but TGP_β1 mRNA and protein,Col_Ⅳand PN protein expression significantly increased in model group( mRNA:0. 43 ± 0. 17 vs. 1. 00 ± 0. 00,0. 34 ± 0. 08 vs. 1. 00 ± 0. 00,2. 97 ± 0. 54 vs. 1. 00 ± 0. 00,all P〈0. 05;protein:0. 25 ± 0. 10 vs. 0. 51 ± 0. 06,0. 24 ± 0. 07 vs. 0. 58 ± 0. 04,0. 59 ± 0. 09 vs. 0. 33 ± 0. 06,16. 01 ± 0. 87 vs. 8. 79 ± 0. 39,14. 64 ± 0. 32 vs. 9. 36 ± 0. 59,all P〈0. 05);com_pared with model group,the mRNA and protein expressions of RARα,DHB,TGP_β1 and Col_Ⅳand PN protein ex_pression had no significant difference in negative control group(all P〉0. 05);compared with model group,the mRNA and protein expression of RARα,DHB mRNA and protein expression significantly increased,but the TGP_β1 mRNA and protein,Col_Ⅳ and PN protein expression significantly decreased in transfected group( mRNA:0. 86 ± 0. 07 vs. 0. 43 ± 0. 17,0. 89 ± 0. 11 vs. 0. 34 ± 0. 08,1. 65 ± 0. 28 vs. 2. 97 ± 0. 54,all P〈0. 05;protein:0. 40 ± 0. 07 vs. 0. 25 ± 0. 10,0. 45 ± 0. 10 vs. 0. 24 ± 0. 07,0. 43 ± 0. 08 vs. 0. 59 ± 0. 09,11. 57 ± 0. 33 vs. 16. 01 ± 0. 87,11. 67 ± 0. 53 vs. 14. 64 ± 0. 32,all P〈0. 05).(3)Correlation analysis revealed that RARα protein expression was negatively correlated with RIP index,Col_Ⅳ,PN,TGP_β1(r﹦ _0. 78,_0. 78,_0. 76,_0. 76,all P〈0. 05);DHB protein expression was negatively correlated with RIP index,Col_Ⅳ,PN,TGP _β1( r ﹦ _0. 87,_0. 87,_0. 88,_0. 75,all P 〈0. 05);RARα protein was positively correlated with DHB(r﹦0. 85,P〈0. 05). Conclusion Overexpression of RARα could attenuate RIP by enhancing DHB expression in rats subjected to unilateral ureteral obstruction.

Effect of overexpression of retinoic acid receptor α on epithelial -to -mesenchymal transition induced by hypoxia in renal tubular epithelial cells / 中华实用儿科临床杂志

Objective To explore the effect of overexpression of retinoic acid receptor α(RARα)on epithelial-to-mesenchymal transition(EMT)induced by hypoxia in renal tubular epithelial cells(NRK-52E).Methods The RARα lentivirus vector and negative control lentivirus vector were synthetised.The NRK-52E cells were divided into 4 groups:the normal control group,the hypoxia model group,the transfection group and the negative control group.Puro-mycin(2 mg/L)was added in transfection group and negative control group for screening after gene interference for 72 h.Then the 2 groups were subjected to hypoxia/reoxygenation,but the normal control group had no treatment. The change of cellular morphology was observed by using light microscope;the mRNA and protein expressions of RARα, E-cadherin,α -smooth muscle actin(α-SMA)in NRK-52E cells were detected by adopting reverse transcription-polymerase chain reaction(RT-PCR)and Western blot after hypoxia for 48 h.Results (1)Light microscope re-vealed that cells in both hypoxia model group and negative control group cells became atrophic and elongated,which were consistent with the morphology of myofibroblasts.But cells in transfection group cells were cubic,forming an epi-thelial monolayer.(2)Compared with the normal control group,the mRNA and protein expressions of RARα and E-cadherin in hypoxia model group were dramatically reduced(mRNA:0.58 ± 0.12 vs.1.00 ± 0.00,0.11 ± 0.00 vs. 1.00 ± 0.00,t= -0.63,767.30,all P<0.05;protein:0.63 ± 0.12 vs.1.62 ± 0.16,0.44 ± 0.22 vs.1.27 ± 0.08,t=8.61,6.19,all P<0.05),but the mRNA and protein expressions of α-SMA were higher(3.47 ± 0.83 vs.1.00 ± 0.00,1.39 ± 0.16 vs.0.64 ± 0.10,t= -5.01,-6.91,all P<0.05).(3)The mRNA and protein expressions of RARα and E-cadherin in the transfection group were significantly increased,compared with hypoxia model group(mRNA:4.69 ± 1.34 vs.0.58 ± 0.12,0.23 ± 0.00 vs.0.11 ± 0.00,q=9.13,25.48,all P<0.05;protein:1.39 ± 0.19 vs. 0.63 ± 0.12,0.87 ± 0.09 vs.0.44 ± 0.22,q=7.92,4.30,all P<0.05)and negative control group(mRNA:4.69 ± 1.34 vs.0.55 ± 0.21,0.23 ± 0.00 vs.0.12 ± 0.01,q=9.20,23.35,all P<0.05;protein:1.39 ± 0.19 vs.0.65 ±0.18,0.87 ± 0.09 vs.0.39 ± 0.21,q=7.71,4.80,all P<0.05).Conversely,the mRNA and protein levels of α-SMA were obviously lower in transfection group(1.52 ± 0.34 vs.3.47 ± 0.83,4.05 ± 0.81,0.82 ± 0.13 vs.1.39 ± 0.10,1.17 ± 0.10,q=4.88,6.33,7.50,4.61,all P<0.05).The difference in mRNA and protein expressions of RARα,E-cadherin,α-SMA between the hypoxia group and the negative control group had no statistical significance (all P>0.05).Conclusion Overexpression of RARα could alleviate EMT of renal tubular epithelial cells induced by hypoxia.

Effects of RARG on viability and migration ability of gastric cancer cells / 中国病理生理杂志

AIM:To investigate the effect of retinoic acid receptor gamma(RARG)on the viability and migra-tion ability of gastric cancer cells.METHODS:The expression of RARG in gastric cancer and normal gastric tissues and its correlation with the overall survival rate of gastric cancer patients were analyzed by bioinformatics.The expression of RARG was promoted and inhibited by over-expression plasmid transfection and RNA interference technique in gastric can-cer cells in vitro,respectively.MTT and Transwell assays were used to detect the effect of RARG on the viability and mi-gration ability of gastric cancer cells.The effect of RARG on regulating the Wnt/β-catenin signaling pathway was evaluated by Western blot and TOP/FOP dual-luciferase reporter assay.The protein interaction of RARG and β-catenin was deter-mined by co-immunoprecipitation and immunofluorescence co-localization assay.RESULTS:Over-expression of RARG en-hanced the viability and migration ability of gastric cancer SGC 7901 cells(P<0.05).Knockdown of RARG attenuated the viability and migration ability of gastric cancer MGC-803 cells(P<0.05).At the same time, RARG over-expression in-creased the protein expression levels of β-catenin, c-Myc, cyclin D1, Twist and Snail(P<0.05), and the activity of TOP/FOP dual-luciferase reporter gene(P<0.05).In addition, RARG interacted with β-catenin protein in the gastric cancer cells.CONCLUSION:RARG promotes the viability and migration ability of gastric cancer cells via activating the Wnt/β-catenin signaling pathway,thus playing an important role in the development of gastric cancer.

Research progress on the involvement of nuclear receptor in regulating autophagy / 生物医学工程学杂志

Nuclear receptors are transcriptional regulators involved in almost all biological processes such as cell growth, differentiation, apoptosis, substance metabolism and tumor formation, and they can be regulated by small molecules that bind to them. Autophagy is a special way of programmed cell death and it is a highly conserved metabolic process. Once autophagy defects or excessive autophagy occur, the disease will develop. In recent years, numerous studies have shown that nuclear receptors are related to autophagy. Therefore, this paper mainly reviews the research progress on nuclear receptors involved in the regulation of autophagy, and focuses on the mechanism of several nuclear receptors involved in the regulation of autophagy, aiming at understanding the molecular basis of how nuclear receptors participate in regulating autophagy, as well as providing possible ideas and strategies for the treatment of corresponding diseases.

Retinoic acid affects apoptosis of neurons injured by hypoxic-ischemic brain damage via retinoic acid receptor alpha / 中华物理医学与康复杂志

Objective To explore the effect of the retinoic acid (RA) on the apoptosis of neurons caused by hypoxic ischemic brain damage (HIBD).Methods Seventy-two newborn Sprague-Dawley rats were randomly divided into an RA deficiency (RAD) group,an RA normal (RAN) group and a control group,each of 24.The HIBD model was established in the RAD and RAN groups using Rice's method.The left common carotid artery was exposed,ligated and cut,inducing hypoxia.In the control group the left common carotid artery was exposed without any other treatment.Three and 7 days after the operation,neuron apoptosis in the brain tissue was evaluated using TUNEL staining.The degree of HIBD was quantified using modified neurological severity scores (mNSS) 7,14,21 and 28 days after the operation.Primary neurons were cultured in vitro,and oxygen glucose deprivation (OGD) was induced,then control,OGD and RA+ OGD groups were formed.The gene transcription and the protein activity of retinoic acid receptor alpha (RARcα),GDNF (glial cell line-derived neurotrophic factor) and Caspase-8 were examined with polymerase chain reactions (PCR) and Western blotting.The RA+OGD group was exposed to RA and SiRNA adenovirus,and divided into a silenced group and a negative transfection group according to the infection.Results The average mNSS of the RAD group was significantly higher than that of the RAN group.TUNEL staining showed that the apoptotic cells in the cortex increased from day 3 to 7 after the operation,but significantly more in the RAD group than in the RAN group.The gene transcription and protein activity of RARα and GDNF in the RA+OGD group were significantly higher than in the OGD group,and those of Caspase-8 were significantly lower.The gene transcription and protein activity of RARα and GDNF in the silenced group were significantly lower than in the negative transfection group,while those of Caspase-8 were just the opposite.Conclusion RA can inhibit the apoptosis of primary neurons after HIBD by up-regulating the expression of GDNF and down-regulating that of Caspase-8 via RARα.

Effect of a tretinoin derivative ECPIRM on retinoic acid receptors and skin irritation responses to it in mice / 中华皮肤科杂志

Objective To estimate the effect of a tretinoin derivative ECPIRM on retinoic acid receptors (RARs),and to observe skin irritation responses to it in mice.Methods Cultured SCL-1 cells were divided into 2 groups to be treated with culture medium containing 10 μmol/L ECPIRM (ECPIRM group) or 10 μmol/L all-trans retinoic acid (ATRA) (ATRA group) for 24 hours,and those treated with drug-free culture medium served as the control group.Western blot analysis and real-time fluorescence-based quantitative PCR were performed to quantify the protein and mRNA expressions of RARs (RARα,RARβ,RARγ and RXRα) respectively.In addition,real-time fluorescence-based quantitative PCR was conducted to measure the mRNA expressions of two target genes of the activated RAR signaling pathway,i.e.,cytochrome P450 26A1 (CYP26A1) and tazarotene-induced gene 1 (TIG1).Eight BALB/c mice were equally divided into 2 groups to be topically treated with 0.075％ ECPIRM gel or 0.05％ ATRA cream at equal molar concentrations on the shaved skin once daily for 21 successive days.Skin irritation reactions were assessed in these mice.Results Compared with the control group,the ATRA group showed significantly increased protein and mRNA expressions of RARα,RARβ and RARγ (all P ＜ 0.05).The mRNA expressions of CYP26A1 and TIG1 genes in the ATRA group were 25.49 and 3.88 times that in the control group respectively (both P ＜ 0.01).However,there was no significant difference in the protein expressions of RARα,RARβ,RARγ and RXRα,or mRNA expressions of RARα,RARβ,RARγ CYP26A1 and TIG1 between the ECPIRM group and control group (all P ＞ 0.05).Obvious Skin irritation reactions such as erythema and desquamation were observed in BALB/c mice after 2-day topical treatment with ATRA cream,and their degree peaked after 5-day treatment.However,neither erythema nor desquamation was observed in BALB/c mice during 21-day treatment with 0.075％ ECPIRM gel.Conclusion Unlike ATRA,ECPIRM cannot activate the canonical RAR signaling pathway or cause skin irritation reactions.

Am80 inhibits neointima hyperplasia by promoting interaction of KLF4 with RARα / 中国病理生理杂志

[ ABSTRACT] AIM:To investigate the inhibitory effect of Am80 on neointima hyperplasia in carotid arteries after balloon injury and to observe the interaction between Krüppel-like factor 4 (KLF4) and retinoic acid receptorα(RARα). METHODS:Neointima hyperplasia in carotid arteries was observed by hemotoxylin and eosin staining.The expression of KLF4 and cyclin D1 was examined by immunostaining and Western blotting analysis.To detect the interaction between KLF4 and RARαin the vascular tissue, the injured arteries were harvested, and the protein extracts were prepared and subjected to co-immunoprecipitation assay.RESULTS:Compared with injured group, Am80 significantly reduced neointi-mal hyperplasia and the thickness ratio of intima to media.Am80 not only up-regulated KLF4 or RARαexpression in caro-tid arteries, but also increased the interaction between KLF4 and RARαat tissue levels.CONCLUSION:Am80 inhibits neointima hyperplasia in carotid arteries after balloon injury by promoting the interaction between KLF4 and RARα.

Location of NLS-RARα protein in peripheral blood tumor cells of patients with acute promyeolic leukemia / 第二军医大学学报

Objective To verify the presence and location of the NLS-RARex protein in the peripheral blood tumor cells of patients with acute promyeolic leukemia (APL). Methods Western blotting analysis was used to identify the NE enzyme in the peripheral blood tumor cells of APL patients. The nucleoprotein in tumor cells was prepared and NLS-RARex protein was detected by Western blotting analysis. The expression and location of NLS-RARex protein in peripheral blood tumor cells of APL patients were examined by FITC/DAPI double immunofluorescence staining and FITC/PI double staining laser confocal microscopy. The expression and location of NLS-RARex protein in NB4 cells infected with recombinant adenovirus Ad-NE was used as positive control and those of wildtype RARex in the neutrophils of healthy controls were taken as negative control. Results Positive control was successfully established. NE enzyme and NLS-RARex protein were expressed in peripheral blood tumor cells of APL patients. Immunofluorescence and laser confocal findings indicated that NL&RARex protein was mainly located at the nuclei of peripheral blood tumors cells in APL patients. Conclusion NLS-RARex protein has been successfully detected by 3 different methods in the peripheral blood tumor cells of APL patients and its intracellular location has also been proposed, which can contribute to the early diagnosis and recurrence monitoring of APL.

Molecular evolution and expression profile of the chemerine encoding gene RARRES2 in baboon and chimpanzee

BACKGROUND: Chemerin, encoded by the retinoic acid receptor responder 2 (RARRES2) gene is an adipocytesecreted protein with autocrine/paracrine functions in adipose tissue, metabolism and inflammation with a recently described function in vascular tone regulation, liver, steatosis, etc. This molecule is believed to represent a critical endocrine signal linking obesity to diabetes. There are no data available regarding evolution of RARRES2 in non-human primates and great apes. Expression profile and orthology in RARRES2 genes are unknown aspects in the biology of this multigene family in primates. Thus; we attempt to describe expression profile and phylogenetic relationship as complementary knowledge in the function of this gene in primates. To do that, we performed A RT-PCR from different tissues obtained during necropsies. Also we tested the hypotheses of positive evolution, purifying selection, and neutrality. And finally a phylogenetic analysis was made between primates RARRES2 protein. RESULTS: RARRES2 transcripts were present in liver, lung, adipose tissue, ovary, pancreas, heart, hypothalamus and pituitary tissues. Expression in kidney and leukocytes were not detectable in either species. It was determined that the studied genes are orthologous. CONCLUSIONS: RARRES2 evolution fits the hypothesis of purifying selection. Expression profiles of the RARRES2 gene are similar in baboons and chimpanzees and are also phylogenetically related.

Promyelocytic leukemia-retinoic acid receptorαfusion gene:research advances / 国际药学研究杂志

Acute promyelocytic leukemia (APL) is a distinctive subtype of acute myeloid leukemia with a distinct biology and clinical presentation. Its molecular biology characteristic is a aberrant chromosomal translocation of the promyelocytic leukemia (PML) gene on chromosome 15 and the retinoic acid receptor α(RARα) gene on chromosome 17. This translocation generates PML-RARα fusion protein, which plays an important role in the genesis, development, diagnosis and therapy of APL. The PML protein has a close relationship with PML-RARαfusion gene. This article mainly summarizes the character, the function of PML protein and the degradation pathway of PML-RARα.

Progresses on relationship of conotruncal heart defects and retinoic acid signaling pathway / 国际儿科学杂志

Congenital conotruncal heart defects (CHD),including tetralogy of Fallot (TOF),double outlet of right ventricle(DORV),transposition of the great arteries(TGA),persistent truncus arteriosus (PTA),is a variety of common and serious congenital cardiovascular diseases which are threatenting to the health of neonates and infants.Previous studies have demostrated that TBX1 contricuted to some of the CHD.Recent studies have also confirmed that retinoic acid signaling pathway plays a curcial role of development of CHD.Further studies have also found that TGF-β2 differential expression is closely related with phenotypic polymorphism of conotruncal heart defects in retinoic acid receptor mutant mice,of which the mechanism is not yet clear.This paper provides an overview of the relationship between TBX1-RA signaling pathway and congenital conotruncal heart defects and TGF-β2-RA and CHD during the development of CHD.

Promyelocytic leukemia-retinoic acid receptor α fusion gene: Research advances / 国际药学研究杂志

Acute promyelocytic leukemia (APL) is a distinctive subtype of acute myeloid leukemia with a distinct biology and clinical presentation. Its molecular biology characteristic is a aberrant chromosomal translocation of the promyelocytic leukemia (PML) gene on chromosome 15 and the retinoic acid receptor α(RARα) gene on chromosome 17. This translocation generates PML-RARα fusion protein, which plays an important role in the genesis, development, diagnosis and therapy of APL. The PML protein has a close relationship with PML-RARα fusion gene. This article mainly summarizes the character, the function of PML protein and the degradation pathway of PML-RARα.

Influence of retinoic acid receptor-mediated all-trans retinoic acid on renal tissue cell proliferation and apoptosis in rats with diabetic nephropathy / 中华肾脏病杂志

Objective To investigate the influence of retinoic acid receptor (RAR-α,RAR-β and RAR-γ)-mediated all-trans retinoic acid (ATRA) on renal tissue cell proliferation and apoptosis in rats with diabetic nephropathy,and to analysze the possible mechanism. Methods Male SD rats were randomly divided into normal control group (group N,n=10) and diabetic model group (n=20).Diabetes was induced by streptozotocin(STZ) injection.After successful modeling,the model rats were randomly divided into diabetes group (group D,n=10) and ATRA treatment group (group T,n=10).Rats in group T received ATRA 10 mg·kg-1·d-1 by gavage from the 2nd day of successful modeling for 8 or 12 weeks,meanwhile group N and group D received same volume distilled water.In each group,5 rats were sacrificed respectively at the 8th week or the 12th week,then biochemical markers were measured and kidney pathology was examined.Apoptosis index(AI)of renal tissue cells of each group was tested by TUNEL.The expressions of RAR-α,RAR-β and RAR-γ in renal tissues were tested using indirect immunofluorescence.The expressions of type Ⅰ collagen and laminin as proliferation indicators,along with Smac and caspase-3 as the correlated factors of apoptosis in renal tissue of each group were tested by immunohistochemistry staining.The mRNA expressions of Smac and caspase-3 were tested using real-time fluorescence quantitative PCR. Results Compared with group N,24 h urine protein,serum creatinine,blood urea nitrogen,ratio of kidney weight/body weight increased significantly (P＜0.05,respectively) in group D,and further increased with observation time.Compared with the group D,24 h urine protein and ratio of kidney weight/body weight decreased in group T (P＜0.05,respectively).Compared with group D,the group T presented minor pathological changes.TUNEL assay indicated that compared with group N,the group D showed an obvious increase in renal cell apoptosis in time-dependent manner,and the group T showed a decrease compared with the group D (P＜0.01,respectively).Compared with group N,the expression of RAR-α and RAR-β positive cells number in group D were decreased (P＜0.01,respectively).Compared with group D,the expression of RAR-α and BAR-β positive cells number in group T increased (P＜0.01,respectively).Renal tissues of each group did not show expressions of RAR-γ.After 12 weeks,compared with group N,expressions of type-Ⅰ collagen,laminin,Smac and caspase-3 protein in the glomerular mesangial area and basement membrane of renal tissues in group D increased significantly (P＜0.01,respectively),and enhanced with time.Compared with the group D,expressions of type Ⅰ collagen,laminin,Smac and caspase-3 protein in group T decreased (P＜0.01,respectively).Compared with the group N,group D had an obvious increase in the mRNA expressions of Smac and caspase-3,and a significantly decrease in group T (P＜0.01,respectively). Conclusions ATRA may prevent the cell proliferation and apoptosis in diabetic renal tissue through its receptor-mediated pathway,and may protect rats against diabetic nephropathy.

Expression of retinoic acid receptor γ mRNA in blood leukocytes of acute schizophrenic patients / 中华行为医学与脑科学杂志

Objective To study the differences in retinoic acid receptor γ(RARγ) mRNA expression levels in blood leukocytes between antipsychotic-free and antipsychotic-naive schizophrenic patients and healthy control,especially in different genders. Methods Forty-three acute schizophrenic patients who were antipsychotic-naive or antipsychotic-free for at least three months (male = 34, female = 9) and 39 age- and sex-matched healthy subjects (male =25 ,female = 14) were included for blood leukocytes expression of RAR γ mRNA ,using real-time PCR technique. Results Kolmogorov-Smirnov Z analysis showed a significant increase of RARγ mRNA (P =0.041) level in blood leukocytes of pooled schizophrenic patients(0. 027 ± 0. 003) than in the healthy subjects (0. 020 ± 0.002). The elevation was mainly found in the female patients (0. 030 ± 0.003). Within-sex analysis showed that the female schizophrenic patients showed a trend increase (P = 0. 166) of RAR γmRNA expression compared with the male patients (0. 026 ± 0. 001) and exhibited greater RARγ mRNA expression (P = 0. 014)when compared with the female healthy subjects(0. 018 ±0.004). Conclusions The present findings showed an abnormal expression of leukocyte RARγ mRNA level in antipsychotic-free and antipsychotic-naive schizophrenia especially in the female patients. Blood RARγ markers could add to the diagnosis and individualized pharmacotherapy of schizophrenic patients ,especially the female patients.

The Relationship between the Expression of RARα,RARβ,ER, PR and the Endometrial Carcinoma / 实用妇产科杂志

Objective:To evaluate the role of the retinoic acid raceptor α (RARα) , retinoic acid receptor β(RARp) , estrogen receptor(ER) and progesterone receptor(PR) in the clinical pathological stage, histologcal classification and the muscular invasive depth of the endometrial carcinoma through detecting the expression of these receptors.Methods:48 paraffin sections with endometrial carcinoma by pathological conformation ware selected.Immunohistochemistry was used to detect the expression of RARα, RARβ, ER and PR.The relationship between these raceptors and the clinical pathological parameters was evaluated.Results:①The positive expression ratio of the RARα and RARβ were 47.92% (23/48) and 25.00% (12/48) respectively.The level of RARα was higher than that of RARβ (P<0.05).②The expression of RARα in the endometrial carcinoma increased with the increasing of the pathological stage and the decreasing of the histological differentiation (P<0.05).But the expression of these two receptors had no significant relation with the histological classification and the muscular invasive depth (P >0.05).③The level of the RARβ was consistent with that of the ER and PR, and it decreased with the increasing of the malignant extent of the endometrial adenocarcinoma (P < 0.05) ,and had no significant relation with the pathological stage, the histological classification and the muscular invasive depth (P >0.05).④The expression of RARβ was positively correla ted to the expression of ER and PR, but the expression of RARα was negatively correlated to the expression ER and PR.Conclusions :There is expression of RARα、RARβ in endometrial carcinoma, and it has close relationship between the expression of RARα and the development of endometrial carcinoma.The absence of the RARβ expression and the high expression of the RARα are related to the histological classification of endometrial carcinoma.

Verification of interaction between glutamate-ammonia ligase and nuclear localization signal-retinoic acid receptor α protein inside and outside cells / 第二军医大学学报

Objective: To verify the interaction between glutamate-ammonia ligase (GLUL) and nuclear localization signal-retinoic acid receptor α (NLS-RARα) protein by yeast two-hybrid and co-immunoprecipitation method. Methods: The two plasmids expressing NLS-RARα bait-protein and GLUL protein were co-transformed into yeast AH109 to investigate the interaction in vivo. Tagged fusion protein eukaryotic expression vectors were constructed and co-transfected into HEK 293 cells. Co-immunoprecipitation was used to investigate the interaction between NLS-RARα and GLUL in vitro. Results: Positive blue clones were found in the QDO/X-α-gal plate. Eukaryotic expression vectors were co-transfected into HEK 293 cells, then HA-NLS-RARα protein was immunoprecipitated by anti-HA polyclonal antibody, and GLUL-cMyc protein expression was confirmed by Western blotting analysis using anti c-Myc monoclonal antibody. Conclusion: The interaction between NLS-RARα and GLUL has been verified by both yeast two-hybrid and co-immunoprecipitation.

Research on retinoic acid system in retina of guinea pig eyes with form deprivation myopia / 眼科研究

Objective Development of eyeball is visually regulated by messengers that released from the retina, and research demonstrated that retinoic acid (RA) is the only extrinsic biochemical candidate that could act as a growth controller. Present study was designed to evaluate the RA system in retina of guinea pig eye with experimental form deprivation myopia. Methods The form deprivation myopia models were monocularly established in the 24 2-week-old guinea pigs by occluding the lateral eyes using white translucent hemispheres for two weeks, and the fellow eyes were as normal control. Refraction diopter was detected with streak retinoscopy after cycloplegia, and axial length and vitreous depth were calculated with Cinescan A/B ultrasonography before and 2 weeks after experiment. All animals were sacrificed and retina was dissected 2 weeks after experiment. The RA level in retina was delected by High Performance Liquid Chromatography (HPLC). The expressions of RA-binding proteins Ⅰ(CRABP-Ⅰ) and RA receptor-β(RAR-β) protein and mRNA were assayed by Western-blotting and Real-time PCR, respectively. The experiment and use of animals followed the Standard of Association for Research in Vision and Ophthalmology. Results The spherical equivalent refraction was (+ 3. 00 ± 0. 75) D in the model group and (+ 2. 88 ± 0. 67) D in control eyes (t= 0. 672, P ＞ 0. 05), the ocular axial length was (7. 822 ± 0. 083) mm in model group and (7. 791 ±0.073) mm in control eyes before experiment (t = 0. 346, P ＞ 0. 05). In 2 weeks after experiment, the spherical equivalent refraction was (- 3. 82 ± 0. 13) D versus (1. 99 ± 0. 58) D and axial length was (8. 346 ± 0. 047) mm versus (7. 888 ± 0. 042) mm between model eyes and control eyes (t = 8. 376, P ＜ 0. 001; t = 3. 343, P ＜0. 05). No significant difference in the level of RA in retina before and after experiment (1. 394 ±0. 079 μg/g vs 1. 295 ±0. 023 μg/g) (t =0. 897, P ＞0. 05) but obviously elevated after experiment in model eyes compared with control eyes (2. 356 ± 0.098 μg/g vs 1.499 ±0.035 μg/g) (t =4. 934, P ＜0. 01). The expression of CRABP-Ⅰ and RAR-β mirrored these directional changes. Conclusion The RA system in retina is upregulated in the eye of guinea pig with form deprivation myopia. This findings suggests that RA may act as a messenger in the development of experimental myopia.

Modulation of Retinoic Receptor Alpha and Beta and Its Links With Beta-catenin and Caspase-3 After Maternal Exposure to All-trans-retinoic Acid in KM Mouse Fetuses / 生物化学与生物物理进展

Epidemiologic studies suggest that intake of excess all-trans-retinoic acid (RA) during embryogenesis induces various developmental defects and the central nervous system (CNS) represents a major site of the teratogenic action of RA. It is therefore important to understand which parameters are affected early by excessive RA in order to devise and improve protective nutritional strategies. The modulations of beta-catenin and caspase-3 levels were investigated in the KM mouse embryo following maternal treatment with a single oral dose of 30mg/kg body weight of RA during the neurula period. In addition, retinoic receptors (RARs) are key transcription factors regulating gene expression in response to RA-activated signals. So the experiment was designed to evaluate whether the alterations in protein expression of RAR alpha and beta during the time of neural tube closure were induced by excessive RA. Maternal intake of excess RA induced early downregulation of RAR alpha and beta, beta-catenin and caspase-3 expression, which was followed by an increase in their expressive levels in the neural tube tissue of mouse embryos. This finding suggests that the alterations in the expression profile of RAR alpha and beta, beta-catenin and caspase-3 may be implicated in the teratogenesis induced by excess RA in KM mouse embryo.

Role of Retinoic Acid Receptor Antagonist on Immunoglobulin M Synthesis by Cord Blood Lymphocytes / 实用儿科临床杂志

Objective Retinoic acid receptor(RAR?) selective antagonist,Ro41-5253(Ro) was used in the counteract test,to confirm the role of RAR? in enhancement of IgM synthesis in cord blood lymphocytes(CBLs) by retinoic acid(RA).Methods CBLs were cultured in vitro and stimulated with or without RAR? agonist RA and(or) antagonist Ro.The cells were harvested at 24 hours and 48 hours of culture time to measure the levels of gene expression of RARa,IL-4 and IL-6.ELISA was used to measure the concentration of IgM in the supernatant of 5 days culture.Results Ro could inhibit the promotion of RA on IgM synthesis in CBLs.RA could up-(regulate) RAR? gene expression,which could be restrained by Ro.Ro also could counteract the up-regulation of RA on IL-4 and IL-6 gene expression.Conclusion The effect of RA on IgM synthesis in CBLs is modulated by RAR?.