生长抑素阻断瘦素诱导肝星状细胞增殖及基质分泌的分子机制

Investigation into the molecular mechanisms of somatostatin inhibiting the proliferation and extracellular matrix secretion of hepatic stellate cells induced by leptin

目的:研究生长抑素(SS)与酪氨酸蛋白酶1B(PTP1B)对瘦素诱导肝星状细胞(HSC)的增殖和基质蛋白分泌以及对JAK2/STAT3通路的影响。方法:运用MTT法检测各浓度SS对瘦素致激活的HSC细胞增殖的影响;实验分为对照组、瘦素组、瘦素+低浓度SS组、瘦素+高浓度SS组,运用RT-PCR、Western blot、ELISA法分别检测各组PTP1B、TIMP-1、I型胶原蛋白和mRNA以及JAK2/STAT3磷酸化程度。结果 :生长抑素可抑制瘦素致HSC增殖;生长抑素可提高HSC内PTP1B的表达,高剂量生长抑素较低剂量提高明显;并减少TIMP-1mRNA、I型胶原mRNA和蛋白的表达,下调JAK2/STAT3蛋白的磷酸化,同时高剂量生长抑素较之低剂量降低明显。结论:生长抑素能上调瘦素作用下HSC内PTP1B的表达,降低JAK2/STAT3磷酸化,抑制其增殖,减少肝纤维化因子的分泌。

Objective To investigate the influence of somatostatin （SS） and protein tyrosine enzyme 1 B （PTP1B） on the proliferation and the matrix protein secretion and phosphorylation of JAK2/STAT3 of hepatic stellate cells （HSC） induced by leptin. Methods The effect of different concentrations of SS on the proliferation of activatied HSCs induced by leptin was detected with MTT assay. HSCs were divided into control group, leptin group, leptin＋10-7 mol/LSS group, leptin＋10-6 mol/LSS group, TIMP-1, type I collagen and PTP1B protein and mRNA. Phosphorylation of JAK2/STAT3 were detected by RT-PCR, Western bolt and ELISA assay. Results SS could promote leptin-induced proliferation of HSCs in a dose-adependent manner. SS can improve PTP1B protein and mRNA, and higher does of SS could render more increase compared with the lower does. SS could reduce TIMP-1 mRNA, type I collagen mRNA and protein expression, and make the JAK2/STAT3 dephosphorylated, and the higher SS group reduce these factors more obviously than the lower group. Conclusion SS up-regulates PTP1B expression, inhibits JAK2/STAT3 signal transduction, proliferation, and reduces TIMP-1, I collagen expression in actived HSCs induced by leptin.