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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.
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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.
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[ 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.
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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.
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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.
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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.