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【Objective】 To investigate the role of LIF/LIFR/STAT3 pathway in endometrial receptivity in rats with polycystic ovary syndrome (PCOS). 【Methods】 Forty 21-day-old SD female rats were divided into normal (control) group, model group, sham-operation group, and LIF group with 10 rats in each. The rat model of PCOS was constructed by subcutaneous injection of prasterone sodium sulfate at the back of the neck. The serum levels of testosterone (T), glucose and insulin in each group were detected. The morphological changes of the uterus in each group were observed by HE staining, and the morphological changes of endometrium were measured. Immunohistochemistry, Western blotting, and Real-time fluorescence quantitative PCR(qRT-PCR) were used to determine the protein expression and mRNA expression of LIF and STAT3 in rat endometrium. 【Results】 Compared with control group, the levels of integrin avb3, serum T, insulin and glucose in PCOS rats were significantly increased (P=0.000, P=0.000, P=0.001). Supplementation of exogenous LIF could significantly reduce the levels of integrin avb3, serum T, glucose and insulin in PCOS rats (P=0.000, P=0.002, P=0.003, P=0.007). HE results showed that exogenous LIF could reduce uterine cavity and glandular morphology in PCOS rats and increase the equivalent diameter (P=0.000, P=0.000) and area (P=0.000, P=0.000) of uterine glands and glandular cavity, the ratio of glandular interstitial area (P=0.000), and the average endometrial thickness (P=0.006), with statistically significant differences. Immunohistochemistry, Western blotting, and qRT-PCR results showed that the expression levels of LIF and p-STAT3 protein and mRNA in model group were significantly decreased compared with control group. Compared with model group, the protein and mRNA expressions of LIF and p-STAT3 in LIF group were significantly increased (P<0.05). 【Conclusion】 Exogenous LIF supplementation can improve endometrial receptivity in PCOS rats, and its mechanism is related to the LIF/LIFR/STAT3 pathway.
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Pancreatic ductal adenocarcinoma is a highly invasive malignant tumor of the digestive system with an extremely poor prognosis. Leukemia inhibitory factor is an important member of the interleukin-6 family and can regulate multiple physiological processes such as cell differentiation, growth, and renewing. This article reviews the mechanism of action of leukemia inhibitory factor in pancreatic ductal adenocarcinoma and the research advances in leukocyte inhibitory factor-targeted therapy based on literature evidence, and the analysis shows that leukemia inhibitory factor plays an important role in the progression, immune escape, and chemotherapy resistance of pancreatic ductal adenocarcinoma and may gradually become a potential biomarker and therapeutic target for pancreatic ductal adenocarcinoma.
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OBJECTIVE@#To evaluate the effect of Buyang Huanwu Decoction (, BYHWD) on glial scar after intracerebral hemorrhage (ICH) and investigate the underlying mechanism.@*METHODS@#Collagenase type VII (0.5 U) was injected stereotaxically into right globus pallidus to induce ICH model. One hundred and twenty Sprague-Dawley rats were randomly divided into 3 groups according to a random number table, including normal group (n=40), ICH model group (n=40) and BYHWD group (n=40), respectively. After ICH, the rats in the BYHWD group were intragastrically administered with BYHWD (4.36 g/kg) once a day for 21 days, while the rats in ICH group were administered with equal volume of distilled water for 21 days, respectively. Double immunolabeling was performed for proliferating cell nuclear antigen (PCNA)/glial fibrillary acidic protein (GFAP) nuclei. The expression of GFAP and leukemia inhibitory factor (LIF) was evaluated by immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR).@*RESULTS@#The astrocytes with hypertrophied morphology around the hematoma was observed on day 3 after ICH. The number of GFAP positive cells and GFAP mRNA levels increased notably on day 3 and reached the peak on day 14 post-ICH (P<0.01). PCNA+/GFAP+ nuclei were observed around the hematoma and reached the peak on day 14 post-ICH (P<0.01). In addition, LIF-positive astrocytes and LIF mRNA level in the hemorrhagic region increased significantly till day 14 post-ICH (P<0.01). However, BYHWD not only reduced the number of PCNA/GFAP nuclei, but also decreased GFAP and LIF levels (P<0.05).@*CONCLUSIONS@#BYHWD could attenuate ICH-induced glial scar by downregulating the expression of LIF in the rats.
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Leukemia inhibitory factor (LIF) contributes to the neuroprotection by neural stem cells (NSCs) after ischemic stroke. Our aim was to explore whether LIF-transfected NSCs (LIF-NSCs) can ameliorate brain injury and promote neuroprotection in a rat model of cerebral ischemia. To accomplish this goal, we transfected NSCs with a lentivirus carrying the LIF gene to stably overexpress LIF. The LIF-NSCs reduced caspase 3 activation under conditions of oxygen-glucose deprivation in vitro. Transient cerebral ischemia was induced in rats by 2 h of middle cerebral artery occlusion (MCAo), and LIF-NSCs were intravenously injected at 6 h post-ischemia. LIF-NSC treatment reduced the infarction volume and improved neurological recovery. Moreover, LIF-NSCs improved glial cell regeneration and ameliorated white matter injury in the MCAo rats. The NSCs acted as carriers and increased the expression of LIF in the lesions to protect against cerebral infarction, suggesting that LIF-NSCs could be a potential treatment for cerebral infarction.
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Leukemia inhibitory factor (LIF) is a multifunctional secretory cytokine that plays a role in different tumor tissues and cells through janus kinase/signal transducer and activator of transcription 3, phosphatidylinositol 3-kinase, mitogen-activated protein kinase signaling pathways. LIF is highly expressed in colo-rectal cancer, breast cancer, malignant melanoma, nasopharyngeal carcinoma and other malignant tumors. High expression of LIF can promote the development of cancer, increase the ability of tumor invasion and migration, reduce the sensitivity of radiotherapy and chemotherapy, and lead to poor prognosis. Blocking the LIF signaling pathway can inhibit tumor progression, and LIF is expected to become a new target for tumor therapy.
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Leukemia inhibitory factor (LIF)is a multifunctional secretory cytokine that plays a role in different tumor tissues and cells through janus kinase/ signal transducer and activator of transcription 3,phos-phatidylinositol 3-kinase,mitogen-activated protein kinase signaling pathways. LIF is highly expressed in colo-rectal cancer,breast cancer,malignant melanoma,nasopharyngeal carcinoma and other malignant tumors. High expression of LIF can promote the development of cancer,increase the ability of tumor invasion and migration,reduce the sensitivity of radiotherapy and chemotherapy,and lead to poor prognosis. Blocking the LIF signaling pathway can inhibit tumor progression,and LIF is expected to become a new target for tumor therapy.
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Objective To compare the expression of leukemia inhibitory factor (LIF), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) in tissue and fluid samples from patients with endometriosis, and investigate whether LIF and IL-6 regulate VEGF in human endometriotic stromal cells (ESC). Methods The levels of VEGF, LIF, IL-6 in serum, peritoneal fluid of patients with and without endometriosis were measured by ELISA. The mRNA of these three factors in the ectopic and eutopic endometrial tissue and stromal cells were measured by real-time PCR. ESC derived from ovarian endometriomas were cultured using the method of primary cell culture with LIF and IL-6, and the level of VEGF mRNA and protein were measured by the method of real-time PCR and ELISA respectively.Results VEGF and IL-6 concentration were 1.2 and 1.3 times higher in the serum of patients with endometriosis than in the control group [(94±19) versus (78±17) ng/L; (45±14) versus (35±9) ng/L; all P<0.05]. VEGF and IL-6 concentration were 1.2 and 1.4 times higher in the peritoneal fluid of patients with endometriosis than in the control group [(110±25) versus (91±21) ng/L; (69±20) versus (49±15) ng/L; all P<0.05]. VEGF and IL-6 concentrations in peritoneal fluid of patients with endometriosis were 1.2 and 1.5 times higher than in serum (all P<0.01). VEGF, LIF and IL-6 mRNA expression were 2.2, 8.6, 44.7 times higher in ESC compared with the matching eutopic endometrial stromal cells (all P<0.01). LIF and IL-6 mRNA were 2.0 and 64.8 times higher in ectopic endometrial tissue than the matching eutopic endometrial tissue (all P<0.05).ESC cultured with LIF, IL-6 and LIF+IL-6 induce VEGF protein secretion [(106±18), (124±30), (140±27) ng/L] by 1.3 , 1.5 and 1.7 times (all P<0.05). Conclusion Overexpression of LIF and IL-6 may synergistically contribute to upregulation of VEGF in ESC and promote development of endometriosis.
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BACKGROUND: Thin endometrial diseases are a challenge in clinical treatment at present. Scholars have found that bone marrow mesenchymal stem cells (BMSCs) transplantation has its unique curative effect and advantages, but few studies have been conducted on pathway or gene control. OBJECTIVE: To observe the effect of BMSCs transplantation in rats with thin endometrium based on the HOXA10 regulatory network. METHODS: Twenty-one adult female Sprague-Dawley rats of SPF grade (provided by the Animal Experimental Center, Guangzhou University of Chinese Medicine in China) were randomly divided into three groups (n=7/group): control group, model group, and BMSCs group. In the latter two groups, a thin endometrium model was prepared in each rat by filling the uterine cavity with 95％ ethanol. In the control group, normal saline was injected to fill the uterine cavity of rats. After extraction of ethanol or normal saline, the rats in the BMSCs group were injected intrauterinely with 1 mL of BMSCs suspension (1×1010 cells/L) , and those in the control and model groups were given the same volume of normal saline. After two estrous cycles, the uterus of each rat was removed. Hematoxylin-eosin staining was used to measure the thickness of the endometrium. Immunohistochemistry was used to detect the expression of vimentin, keratin, vascular endothelial growth factor, leukemia inhibitory factor and integrin αvβ3. qRT-PCR was used to detect the relative transcription of HOXA10 and miR-196 b. RESULTS AND CONCLUSION: (1) Compared with the control group, the endometrial thickness of the rats were significantly thinner in the model and BMSCs groups (P < 0.05) , while the endometrial thickness in the BMSCs group was thicker than that in the model group (P < 0.05). (2) The mean absorbance values of endometrial vimentin, keratin, vascular endothelial growth factor, leukemia inhibitory factor and integrin αvβ3 were highest in the control group, higher in the BMSCs group and lowest in the model group, and there were significant differences between groups (P < 0.05). (3) The relative transcript level of HOXA10 gene in the model and BMSCs group was significantly lower than that in the control group, while the relative transcript level of HOXA10 gene in the BMSCs group was significantly higher than that in the model group (P < 0.05). The relative transcript level of miR-196 b in the model and BMSCs groups was significantly higher than that in the control group (P < 0.05) , while the relative transcript level of miR-196 b in the BMSCs group was lower than that in the model group (P < 0.05). (4) HOXA10 was negatively correlated with miR-196 b gene, HOXA10 was positively correlated with the protein expression to different extents, and miR-196 b gene was negatively correlated with the protein expression to different extents. These findings suggest that BMSCs transplantation can improve the endometrial thickness and relevant protein levels of thin endometrium rats to some extent, which may be attributed to the negative regulation of HOXA10 gene by miR-196 b, and HOXA10 gene further promotes the expression of vascular endothelial growth factor, leukemia inhibitory factor and integrin αvβ3 proteins.
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Objective To investigate the role of leukemia inhibitory factor (LIF) on retinal photoreceptor cells and the underlying mechanism after light damage.Methods Fifty 5-6 weeks old BALB/c mice were randomly divided into normal control group (10 mice),light damage+LIF group (20 mice) and light damage+PBS group (20 mice).Four days before exposing to light,the right eye of each animal in light damage+LIF group and light damage+PBS group was injected with LIF and PBS,respectively;then the mice in the light damage+LIF group and light damage+PBS group were exposed to 4 000 lx intensity of cool white fluorescent light for 4 hours to establish the experimental model of retinal light damage.The function and morphology of retinal photoreceptor cells were detected by flash electroretinogram (fERG) and histopathological examination.Real-time PCR was used to detect the mRNA expression of Jak3,STAT3,and apoptosis-related factor Bcl-2 and Bax.The use of animals is guided by the State Science and Technology Commission's regulations on the management of experimental animals.Results The amplitudes of scotopic ERG a wave of 0.01,1,100,200,400 cd · s/m2 light in the light damage + PBS group were significantly lower than those in the normal control group and light damage + LIF group (all at P ＜ 0.05).The amplitudes of photopic ERG b wave of different color light in the light damage+PBS group were significantly lower than those in the normal control group and light damage+LIF group (all at P＜0.05).The number of photoreceptor nuclei in the light damage+PBS group was significantly lower than that in the normal control group and light damage+ LIF group (both at P＜0.05).Compared with light damage+PBS group,the relative expression of Jak3,STAT3,Bcl-2 mRNA in light damage+LIF group were significantly increased (all at P＜0.05),and the relative expression of Bax mRNA were significantly decreased (P＜0.05).Conclusions LIF can protect retinal photoreceptor cells from light damage,which may result from the activation of Jak3/STAT3 signaling pathway and inhibition of its downstream Bax/Bcl-2 apoptotic pathway.
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Objective To investigate the protective role of light preconditioning in retinal photoreceptor cells and the underlying mechanisms after light damage.Methods Together 42 BALB/c mice were randomly divided into normal control group,light damage group,light preconditioning + light damage group and light preconditioning group.Mice in the light damage group were exposed to 4000 Lux intensity of cool white fluorescent light for 4 h continually;mice in the light reconditioning + light damage group were maintained in 600 Lux cyclic bright light for preconditioning (12 h ON and 12 h OFF) for 6 days,and then exposed to 4000 Lux bright-light for the induction of the damage;mice in the light reconditioning group were maintained in 600 Lux cyclic bright light for preconditioning (12 h ON and 12 h OFF) for 2 days,4 days,6 days.Then the function and morphology of retinal photoreceptor cells were detected by flash electroretinogram (FERG) and histopathological examination in the normal control group,light damage group and light preconditioning + light damage group,while real-time polymerase chain reaction (PCR) was used to detect the mRNA relative expression of leukemia inhibitory factor (LIF) and Western blot analysis was used to detect the phosphoprotein relative expression of signal transducer and activator of transcription 3(STAT3) in the light preconditioning group.Results FERG results showed the amplitudes of scotopic ERG a wave of the light damage group were decreased when compared with the normal control group,with significant difference (P =0.000).Compared with the light damage group,the amplitudes of scotopic ERG a wave of the light preconditioning + light damage group were increased significantly (P =0.000).Histopathological examination results showed that the number of photoreceptor nuclei in the light damage group was decreased compared with the normal control group,and the difference was statistically significant (P =0.000).Compared with light damage group,the number of photoreceptor nuclei in light preconditioning + light damage group was increased significantly (P =0.000).Real-time PCR results showed light preconditioning enhanced the LIF mRNA relative expression in a time-dependent manner (F=128.776,P =0.000).Western blot results showed light preconditioning up-regulated the phosphoprotein relative expression of STAT3 protein in a time-dependent manner (F =73.493,P =0.000).Conelusion Light preconditioning can protect retinal photoreceptor cells against light damage which may results from the activation of LIF/STAT3 signaling pathway.
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Objective To investigate the role of leukemia inhibitory factor (LIF) in cell survival of cone photoreceptors and the underlying mechanism following oxidant injury.Methods 661W cells were cultured and randomly divided into normal control group,LIF intervention group,H2O2 intervention group,S3 I201 intervention group,H2O2 + LIF intervention group,H2O2 + S3I201 intervention group and H2O2 + LIF + S3I201 intervention group,according to the different intervention drugs.MTT assay and Western blot were used to detect the effects of LIF pretreatment on 661W activity and the expression of STAT3 protein and its phosphorylation level after oxidative damage.Using STAT3-specific inhibitor S3I201 to block the STAT3 signal transduction pathway,MTT assay and real-time PCR were used to detect the effects of STAT3 signaling pathway on 661 W activity and the mRNA expression of survivin bcl-2 and bcl-xi after oxidative damage.Results Compared to H2O2 intervention group,the relative protein expression of p-Tyr705-STAT3 was increased in H2O2 + LIF intervention group,the difference was statistically significant (P ＜ O.05);The relative protein expression of p-Tyr705-STAT3 was decreased in H2O2 + S3I201 intervention group,the difference was statistically significant (P ＜ 0.05).Compared to H2O2 intervention group,the cell activity of 661W cells was increased in H2O2 + LIF intervention group,the difference was statistically significant(P ＜0.05).Compared to H2O2 + LIF intervention group,the cell activity of 661W cells was decreased in H2O2 + LIF + S3I201 intervention group,the difference was statistically significant (P ＜ 0.05).Compared to normal control group,the mRNA expression of bcl-2 and bcl-xl were increased in LIF intervention group,H2O2 intervention group and H2O2 + LIF intervention group,the differences were statistically significant (all P ＜ 0.05).Compared to H2O2 + LIF intervention group,the mRNA expression of bcl-2 and bcl-xl were decreased in H2O2 + LIF + S3I201 intervention group,the differences were statistically significant (all P ＜ 0.05).Conclusion LIF has protective effect on oxidative injury of cone photoreceptors,and it may contribute to cell survival through activation of the STAT3 signaling transduction pathway and its related survivin.
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The distal cytoplasmic motifs of leukemia inhibitory factor receptor α-chain (LIFRα-CT3) can independently induce intracellular myeloid differentiation in acute myeloid leukemia (AML) cells by gene transfection; however, there are significant limitations in the potential clinical use of these motifs due to liposome-derived genetic modifications. To produce a potentially therapeutic LIFRα-CT3 with cell-permeable activity, we constructed a eukaryotic expression pcDNA3.0-TAT-CT3-cMyc plasmid with a signal peptide (ss) inserted into the N-terminal that codes for an ss-TAT-CT3-cMyc fusion protein. The stable transfection of Chinese hamster ovary (CHO) cells via this vector and subsequent selection by Geneticin resulted in cell lines that express and secrete TAT-CT3-cMyc. The spent medium of pcDNA3.0-TAT-CT3-cMyc-transfected CHO cells could be purified using a cMyc-epitope-tag agarose affinity chromatography column and could be detected via SDS-PAGE, with antibodies against cMyc-tag. The direct administration of TAT-CT3-cMyc to HL-60 cell culture media caused the enrichment of CT3-cMyc in the cytoplasm and nucleus within 30 min and led to a significant reduction of viable cells (P < 0.05) 8 h after exposure. The advantages of using this mammalian expression system include the ease of generating TAT fusion proteins that are adequately transcripted and the potential for a sustained production of such proteins in vitro for future AML therapy.
Subject(s)
Animals , Cricetinae , Female , Humans , Cytoplasm/metabolism , Gene Products, tat/metabolism , Leukemia Inhibitory Factor Receptor alpha Subunit/metabolism , Chromatography, Affinity , Cell Differentiation/genetics , Cytoplasm/genetics , Electrophoresis, Polyacrylamide Gel , Genetic Vectors , Gene Products, tat/genetics , Leukemia Inhibitory Factor Receptor alpha Subunit/genetics , TransfectionABSTRACT
Leukemia inhibitory factor(LIF) is a multifunctional cytokine.In recent years,investigations have made some advancement in the effect of LIF on central nervous system.LIF shows a high expression in various central nervous system diseases and related animal models,which shows a neuroprotective effect most time in central nervous system injuries.LIF is defined as a neurotrophic factor.It might provide a new strategy for the therapy of central nervous system diseases to undertake further studies on leukemia inhibitory factor and central nervous system diseases.
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Skin-derived precursor cells (SKPs) are multipotent, sphere-forming and embryonic neural crest-related precursor cells that can be isolated from dermis. It is known that the properties of porcine SKPs can be enhanced by leukemia inhibitory factor (LIF) which is an essential factor for the generation of embryonic stem cells in mice. In our present study, to enhance or maintain the properties of murine SKPs, LIF was added to the culture medium. SKPs were treated with 1,000 IU LIF for 72 hours after passage 3. Quantitative real time RT-PCR was then performed to quantify the expression of the pluripotent stem cell specific genes Oct4, Nanog, Klf4 and c-Myc, and the neural crest specific genes Snai2 and Ngfr. The results show that the expression of Oct4 is increased in murine SKPs by LIF treatment whereas the level of Ngfr is decreased under these conditions. Interestingly, LIF treatment reduced Nanog expression which is also important for cell proliferation in adult stem cells and for osteogenic induction in mesenchymal stem cells. These findings implicate LIF in the maintenance of stemness in SKPs through the suppression of lineage differentiation and in part through the control of cell proliferation.
Subject(s)
Animals , Mice , Adult Stem Cells , Cell Proliferation , Dermis , Durapatite , Embryonic Stem Cells , Leukemia , Leukemia Inhibitory Factor , Mesenchymal Stem Cells , Neural Crest , Pluripotent Stem CellsABSTRACT
PURPOSE: This study was performed to determine whether the serum concentrations of interleukin (IL)-6 family cytokines are elevated in patients with rheumatoid arthritis (RA) and to investigate the relationship between IL-6 family cytokine levels and disease activity in RA patients. MATERIALS AND METHODS: We obtained serum samples from 40 patients with RA and 40 age- and sex-matched healthy controls, and we assessed the clinical parameters of disease activity, including the 28-joint disease activity score (DAS28) and C-reactive protein (CRP) levels. Serum samples from five patients with high disease activity (DAS28 > 5.1) were also collected at the eighth week of treatment. Serum concentrations of IL-6, IL-11, and leukemia inhibitory factor (LIF) were measured using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum concentrations of IL-6 family cytokines, including IL-6, IL-11, and LIF, were significantly elevated in patients with RA compared to those of healthy controls. Although there was no significant relationship between IL-6 family cytokine levels and DAS28, the IL-6 levels of patients with RA showed a significant correlation with CRP levels. After eight weeks of medical treatment in patients with high disease activity, a decrease in DAS28 was associated with a significant decrease in the serum concentrations of IL-6 and IL-11. CONCLUSION: The serum concentrations of IL-6 family cytokines were significantly elevated in patients with RA, and they decreased with medical treatment. These findings suggest a possible role for IL-6 family cytokines in the pathogenesis of RA.
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Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Arthritis, Rheumatoid/blood , C-Reactive Protein/analysis , Cytokines/blood , Enzyme-Linked Immunosorbent Assay , Interleukin-11/blood , Interleukin-6/blood , Leukemia Inhibitory Factor/bloodABSTRACT
Objective: To investigate the regulatory effect of dissociative intracytoplasmic domain of leukemia inhibitory factor receptor a (LIFRα) subunit on the growth of HL-60 cells and the related signal transduction mechanism. Methods: The constructed recombinant plasmids pcDNA3. 0-190CT2 + 3 and cDNA3. 0-190CT3 were identified and transfected into HL-60 cells with liposome FuGene-6. Then the cells were cultured in a medium containing G-418 and the positive clones were selected. Immunohistochemical method and Western blotting were used to detect the expression of the target protein in HL-60 cells and the growth curve of the cells was plotted. The expression of proliferating cell nuclear antigen (PCNA) and the phosphorylation levels of signal transducer and activator of transcription 3 (Stat3) were assayed by Western blotting. Results: Western blotting detected the band of target protein and the cell line stably expressing the target protein was obtained. Compared with that of the wild type group, the cell sizes in 190CT2+3 and 190CT3 group were enlarged. The ratio of leaf cell number to the total cell number increased and the cell proliferation was slowed down. We also found that the expression of PCNA was decreased and the phosphorylation level of STAT3 was increased. Conclusion: The dissociative intracytoplasmic domain of LIFRα subunit can accelerate the differentiation of HL-60 cells, inhibit the proliferation of HL-60 cells, and activate signal molecule STAT3.
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Objective: To investigate the effect of the cytoplasmic domain of leukemia inhibitory factor (LIF) receptor α submit, gp190CT3, on activation of the JAK/STAT3 signal transduction pathway and on promotion of leukemia cell HL-60 differentiation into granulocytes. Methods: pcDNA3, 0-gp190CT3 was used to transfect CHO cells. Using immunofluorescent cytochemistry, RT-PCR and flow cytometry techniques, we detected the expression of gp190CT3 gene and protein in the stably-transfected CHO cells. Then the stably-trasfected CHO cells were co-cultured with HL-60 cells and the morphological changes of the HL-60 cells were observed, the levels of STAT3 phosphorylation and the expression of the cell surface antigen CD15 were also determined. Results: Expression of gp190CT3 gene was found in pcDNA3. 0-gp190CT3 transfected CHO cells and gp190CT3-stably-transfect CHO cells were obtained. Compared with the untreated HL-60 cells, the size of the co-cultured HL-60 cells was increased, the morphology was irregular and the level STAT3 phosphorylation and the expression of CD15 were increased. Conclusion: The LIF receptor α submit gp190CT3 participates in the activation of JAK/STAT3 signal transduction pathway and regulates HL-60 cell differentiation and proliferation.
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In order to observe the effect of Bushenantai recipe on the expression of endometrial leukemia-inhibitory factor (LIF) in mice with embryonic implantation dysfunction (EID), 120 Kun- ruing mice post coition were randomized into three groups: normal control group, model group and traditional Chinese medicine group (TCM group) (n=40 in each group). Uterus was collected on the pregnancy day (Pd) 4, 5, 6 after an intravenous injection of Evan's blue. The endometrium was dyed by Evan's blue and the mean points of response were observed on Pd 5. The expression of LIF mRNA and protein was detected by RT-PCR and immunohistochemistry respectively and analyzed statistically by image system. The results showed that the number of implantation sites in model group was remarkably less than in normal control group and TCM group. There was no significant difference between normal control group and TCM group. The expression of L1F mRNA and protein in model group was delayed. Bushenantai recipe could increase the expression of LIF mRNA and protein in endometria of mice with EID. It was suggested that Bushenantai recipe could improve em- bryo implantation of mice with EID by promoting the endometrial LIF expression and endometrial decidualization.
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OBJECTIVE: Uterine leiomyomas are the most common tumor of the uterus. But the molecular causes of uterine leiomyoma remain unclear. We conducted the current investigation in order to elucidate the molecular mechanisms in the development of uterine leiomyoma. METHODS: We employed a new and accurate reverse transcription-polymerase chain reaction (RT-PCR) method that involved annealing control primers (ACPs) to identify the genes that are differently expressed in uterine leiomyoma. RESULTS: Using 120 ACPs, we identified and sequenced 14 differently expressed genes (DEGs) in uterine leiomyoma compared with normal myometrium. Basic Local Alignment Search Tool (BLAST) searches were performed to examine the known functions of these genes associated with uterine leiomyoma. We confirmed differently expressed patterns in more cases using the RT-PCR method. We also detected two novel genes, Tenascin-X and Leukemia Inhibitory Factor Receptor (LIFR), which had not yet been reported to have any functions associated with uterine leiomyoma. RT-PCR confirmation shows that both of these two genes are down-regulated in uterine leiomyoma. CONCLUSION: Our results suggest that Tenascin-X and LIFR may play a role in the development of uterine leiomyoma. Although further studies are required to establish the precise mechanisms with which these genes are involved in the genesis of uterine leiomyoma, the present research is significant in that it is the first study which detects down-regulated novel genes in uterine leiomyoma using the ACP system.
Subject(s)
Animals , Female , Mice , Leiomyoma , Leukemia , Leukemia Inhibitory Factor , Myometrium , Receptors, OSM-LIF , Tenascin , UterusABSTRACT
In order to investigate the expression of leukemia inhibitory factor (LIF) in airway epithelial tissues of normal and asthmatic rats, the influence of dexamethasone and the role of LIF in pathogenesis of asthma, 30 Sprague-Dawley (SD) rats were randomly divided into 3 groups (10 for each group): normal group, asthma model group, and dexamethasone-interfered group. In asthmamodel group and dexamethasone-interfered group, asthma rat models were established by intraperitoneal (i.p.) injection of 10% ovalbumin (OVA) and challenge with 1% OVA via inhalation. Rats in dexamethasone-interfered group were pretreated with dexamethasone (2 mg/kg, i.p) 30 min before each challenge. The expression of LIF protein in lung was detected by immunohistochemistry. The results showed that LIF protein was mainly expressed in cytoplasm of bronchial epithelial cells. The expression of LIF protein in the airway epithelial tissue of asthma model group was significantly higher than that in normal group and dexamethasone-interfered group (P＜0.01), but there was no significant difference between normal group and dexamethasone-interfered group (P＞0.05). It was concluded that the expression of LIF was increased significantly in the airway epithelial tissue of the asthma rats, and dexamethasone could down-regulate the expression of LIF. It was suggested that LIF might play an important role in the pathogenesis of asthma as an inflammation regulator.