BACKGROUND: We previously showed that insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) is a novel mediator in liver fibrosis. Transforming growth factor beta 1 (TGF beta 1) is known as the stron...BACKGROUND: We previously showed that insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) is a novel mediator in liver fibrosis. Transforming growth factor beta 1 (TGF beta 1) is known as the strongest effector of liver fibrosis. Therefore, we aimed to investigate the detailed interaction between IGFBPrP1 and TGF beta 1 in primary hepatic stellate cells (HSCs). METHODS: We overexpressed TGF beta 1 or IGFBPrP1 and inhibited TGF beta 1 expression in primary HSCs for 6, 12, 24, 48, 72, and 96 hours to investigate their interaction and observe the accompanying expressions of a-smooth muscle actin (alpha-SMA), collagen I, fibronectin, and phosphorylated-mothers against decapentaplegic homolog 2/3 (p-Smad2/3). RESULTS: We found that the adenovirus vector encoding the TGF beta 1 gene (AdTGF beta 1) induced IGFBPrP1 expression while that of alpha-SMA, collagen I, fibronectin, and TGF beta 1 increased gradually. Concomitantly, AdIGFBPrP1 upregulated TGF beta 1, alpha-SMA, collagen I, fibronectin, and p-Smad2/3 in a time-dependent manner while IGFBPrP1 expression was decreased at 96 hours. Inhibition of TGF beta 1 expression reduced the IGFBPrP1-stimulated expression of alpha-SMA, collagen I, fibronectin, and p-Smad2/3. CONCLUSIONS: These findings for the first time suggest the existence of a possible mutually regulation between IGFBPrP1 and TGF beta 1, which likely accelerates liver fibrosis progression. Furthermore, IGFBPrP1 likely participates in liver fibrosis in a TGF beta 1-depedent manner, and may act as an upstream regulatory factor of TGF beta 1 in the Smad pathway.展开更多
Background： Endometriosis （EMs） is a common gynecological disorder characterized by endometrial-like tissue outside the uterus. Hypoxia induces the expression of many important downstream genes to regulate the impl...Background： Endometriosis （EMs） is a common gynecological disorder characterized by endometrial-like tissue outside the uterus. Hypoxia induces the expression of many important downstream genes to regulate the implantation, survival, and maintenance ofectopic endometriotic lesions. Transtbrming growth factor-beta I （TGF-β1） plays a major role in the etiology of EMs. We aimed to determine whether TGF-β1 affects EMs development and progression and its related mechanisms in hypoxic conditions. Methods： Endometrial tissue was obtained from women with or without EMs undergoing surgery from October, 2015 to October, 2016. Endometrial cells were cultured and then exposed to hypoxia and TGF-β1 or TGF-β1 inhibitors. The messenger RNA （mRNA） and protein expression levels ofTGF-β1, vascular endothelial growth fhctor （VEGF）, and hypoxia-inducible fhctor-Ic~ （HIF-β1） were measured. A DuaI-Luciferase Reporter Assay was used to examine the effect ofTGF-[31 and hypoxia on a VEGF promoter construct. Student＇s t-test was pertbrmed/br comparison among groups （one-sided or two-sided） and a value ofP 〈 0.05 was considered statistically significant. Results： TGF-β1, VEGF, HIF-β1 mRNA, and protein expression were significantly higher in EMs tissue than that in normal endometrial tissue （t = 2.16, P = 0.042）. EMs primary cultured cells exposed to hypoxia expressed 43.8% higher VEGF mRNA and protein （t = 6.84, P - 0.023）. VEGF mRNA levels increased 12.5% in response to TGF-β1, whereas the combined treatment of hypoxia/TGF-β1 resulted in a much higher production （87.5% increases） of VEGF. The luciferase activity of the VEGF promoter construct was increased in the presence of either TGF-β1 （2.6-fold, t = 6.08, P = 0.032） or hypoxia （11.2-fold, t = 32.70, P 〈 0.001 ）, whereas the simultaneous presence of both stimuli resulted in a significant cooperative effect （ 18.5-fold, t = 33.50, P 〈 0.001 ）. Conclusions： The data support the hypothesis that TGF-β1 is involved in the pathogenesis of EMs through regulating VEGF expression. An additive effect of TGF-[31 and hypoxia is taking place at the transcriptional level.展开更多
目的:通过观察全反式维甲酸对慢性酒精性肝损伤大鼠肝脏TGF-β1、CTGF和Collal表达的影响,探讨该药物对酒精性肝纤维化形成的作用．方法:大鼠24只随机分为3组:酒精组(J组),给予酒精-玉米油混悬液灌胃;治疗组(A组),给予上述混悬液灌胃8 w...目的:通过观察全反式维甲酸对慢性酒精性肝损伤大鼠肝脏TGF-β1、CTGF和Collal表达的影响,探讨该药物对酒精性肝纤维化形成的作用．方法:大鼠24只随机分为3组:酒精组(J组),给予酒精-玉米油混悬液灌胃;治疗组(A组),给予上述混悬液灌胃8 wk后加用0,15 mg／(kg·d) 的全反式维甲酸灌胃;对照组(N组),给予等量的生理盐水和玉米油灌胃．16 wk后处死大鼠．光、电镜下观察肝组织病理改变,高压液相色谱法(HPLC)测肝组织中维甲酸的含量,免疫组化法检测肝组织中转化生长因子β1(TGF-β1)和结缔组织生长因子(CTGF)的蛋白水平,逆转录聚合酶链反应(RT-PCR)检测肝组织中TGF-β1、CTGF和Ⅰ型胶原前胶原α1(Collal)的mRNA水平．结果:光镜下酒精组及治疗组均呈不同程度的酒精性肝炎改变,电镜下酒精组肝细胞线粒体肿胀,内质网扩张,脱颗粒,而治疗组改变轻于酒精组．肝组织中维甲酸含量:酒精组低于正常组,治疗组接近对照组水平．Collal 的mRNA表达在酒精组中较对照组明显增高 (0．18±0．03 vs 0．10±0．02,P<0．01),治疗组较酒精组表达下降(0．14±0．03 vs 0．18±0．03,P <0．05)．TGF-β1的mRNA及蛋白表达在酒精组中增高(0．53±0．17 vs 0．34±0．05,105．93 ±10．12 vs 149．27±10．17,P<0．01),治疗组相对于酒精组有所下降(0．41±0．06 vs 0．53± 0．17,130．80±6.23 vs 105．93±10．12,P<0．05)． CTGF的mRNA及蛋白表达在酒精组中增高 (0．41±0．13 vs 0．17±0．05,130．84±5．72 vs 158.37±6．64,P<0．05),治疗组对于酒精组有所下降(0.30±0．04 vs 0．41±0．13,149．23± 6．65 vs 130．84±5．72．P<0．05)．结论:小剂量全反式维甲酸通过降低慢性酒精性肝损伤大鼠肝脏致纤维化因子TGF-β1, CTGF和Collal的表达抑制早期酒精性肝纤维化的形成．展开更多
基金supported by a grant from the Shanxi Province Foundation for Returness(2012-4)
文摘BACKGROUND: We previously showed that insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) is a novel mediator in liver fibrosis. Transforming growth factor beta 1 (TGF beta 1) is known as the strongest effector of liver fibrosis. Therefore, we aimed to investigate the detailed interaction between IGFBPrP1 and TGF beta 1 in primary hepatic stellate cells (HSCs). METHODS: We overexpressed TGF beta 1 or IGFBPrP1 and inhibited TGF beta 1 expression in primary HSCs for 6, 12, 24, 48, 72, and 96 hours to investigate their interaction and observe the accompanying expressions of a-smooth muscle actin (alpha-SMA), collagen I, fibronectin, and phosphorylated-mothers against decapentaplegic homolog 2/3 (p-Smad2/3). RESULTS: We found that the adenovirus vector encoding the TGF beta 1 gene (AdTGF beta 1) induced IGFBPrP1 expression while that of alpha-SMA, collagen I, fibronectin, and TGF beta 1 increased gradually. Concomitantly, AdIGFBPrP1 upregulated TGF beta 1, alpha-SMA, collagen I, fibronectin, and p-Smad2/3 in a time-dependent manner while IGFBPrP1 expression was decreased at 96 hours. Inhibition of TGF beta 1 expression reduced the IGFBPrP1-stimulated expression of alpha-SMA, collagen I, fibronectin, and p-Smad2/3. CONCLUSIONS: These findings for the first time suggest the existence of a possible mutually regulation between IGFBPrP1 and TGF beta 1, which likely accelerates liver fibrosis progression. Furthermore, IGFBPrP1 likely participates in liver fibrosis in a TGF beta 1-depedent manner, and may act as an upstream regulatory factor of TGF beta 1 in the Smad pathway.
文摘Background： Endometriosis （EMs） is a common gynecological disorder characterized by endometrial-like tissue outside the uterus. Hypoxia induces the expression of many important downstream genes to regulate the implantation, survival, and maintenance ofectopic endometriotic lesions. Transtbrming growth factor-beta I （TGF-β1） plays a major role in the etiology of EMs. We aimed to determine whether TGF-β1 affects EMs development and progression and its related mechanisms in hypoxic conditions. Methods： Endometrial tissue was obtained from women with or without EMs undergoing surgery from October, 2015 to October, 2016. Endometrial cells were cultured and then exposed to hypoxia and TGF-β1 or TGF-β1 inhibitors. The messenger RNA （mRNA） and protein expression levels ofTGF-β1, vascular endothelial growth fhctor （VEGF）, and hypoxia-inducible fhctor-Ic~ （HIF-β1） were measured. A DuaI-Luciferase Reporter Assay was used to examine the effect ofTGF-[31 and hypoxia on a VEGF promoter construct. Student＇s t-test was pertbrmed/br comparison among groups （one-sided or two-sided） and a value ofP 〈 0.05 was considered statistically significant. Results： TGF-β1, VEGF, HIF-β1 mRNA, and protein expression were significantly higher in EMs tissue than that in normal endometrial tissue （t = 2.16, P = 0.042）. EMs primary cultured cells exposed to hypoxia expressed 43.8% higher VEGF mRNA and protein （t = 6.84, P - 0.023）. VEGF mRNA levels increased 12.5% in response to TGF-β1, whereas the combined treatment of hypoxia/TGF-β1 resulted in a much higher production （87.5% increases） of VEGF. The luciferase activity of the VEGF promoter construct was increased in the presence of either TGF-β1 （2.6-fold, t = 6.08, P = 0.032） or hypoxia （11.2-fold, t = 32.70, P 〈 0.001 ）, whereas the simultaneous presence of both stimuli resulted in a significant cooperative effect （ 18.5-fold, t = 33.50, P 〈 0.001 ）. Conclusions： The data support the hypothesis that TGF-β1 is involved in the pathogenesis of EMs through regulating VEGF expression. An additive effect of TGF-[31 and hypoxia is taking place at the transcriptional level.
文摘目的:通过观察全反式维甲酸对慢性酒精性肝损伤大鼠肝脏TGF-β1、CTGF和Collal表达的影响,探讨该药物对酒精性肝纤维化形成的作用．方法:大鼠24只随机分为3组:酒精组(J组),给予酒精-玉米油混悬液灌胃;治疗组(A组),给予上述混悬液灌胃8 wk后加用0,15 mg／(kg·d) 的全反式维甲酸灌胃;对照组(N组),给予等量的生理盐水和玉米油灌胃．16 wk后处死大鼠．光、电镜下观察肝组织病理改变,高压液相色谱法(HPLC)测肝组织中维甲酸的含量,免疫组化法检测肝组织中转化生长因子β1(TGF-β1)和结缔组织生长因子(CTGF)的蛋白水平,逆转录聚合酶链反应(RT-PCR)检测肝组织中TGF-β1、CTGF和Ⅰ型胶原前胶原α1(Collal)的mRNA水平．结果:光镜下酒精组及治疗组均呈不同程度的酒精性肝炎改变,电镜下酒精组肝细胞线粒体肿胀,内质网扩张,脱颗粒,而治疗组改变轻于酒精组．肝组织中维甲酸含量:酒精组低于正常组,治疗组接近对照组水平．Collal 的mRNA表达在酒精组中较对照组明显增高 (0．18±0．03 vs 0．10±0．02,P<0．01),治疗组较酒精组表达下降(0．14±0．03 vs 0．18±0．03,P <0．05)．TGF-β1的mRNA及蛋白表达在酒精组中增高(0．53±0．17 vs 0．34±0．05,105．93 ±10．12 vs 149．27±10．17,P<0．01),治疗组相对于酒精组有所下降(0．41±0．06 vs 0．53± 0．17,130．80±6.23 vs 105．93±10．12,P<0．05)． CTGF的mRNA及蛋白表达在酒精组中增高 (0．41±0．13 vs 0．17±0．05,130．84±5．72 vs 158.37±6．64,P<0．05),治疗组对于酒精组有所下降(0.30±0．04 vs 0．41±0．13,149．23± 6．65 vs 130．84±5．72．P<0．05)．结论:小剂量全反式维甲酸通过降低慢性酒精性肝损伤大鼠肝脏致纤维化因子TGF-β1, CTGF和Collal的表达抑制早期酒精性肝纤维化的形成．
