胆汁酸对肝星状细胞增殖及细胞动能的调控作用(英文)

Bile acids enhance proliferation and motility of hepatic stellate cell through regulation of p38/JNK signaling

目的探讨胆汁酸如何通过调控肝星状细胞促进肝纤维化发生。方法采用BrdU掺入法测定胆汁酸和TGFβ-1对GFSC-2G细胞增殖的影响;利用Wound-healing检测法判定细胞的移动能力;同时利用Western blotting法检测与胆汁酸共同孵育的GFSC-2G细胞的p38和JNK的表达。结果与50μmol/L甘氨鹅脱氧胆酸(GCDCA)共同孵育后,CFSC-2G细胞增殖明显增加,为对照组的152.0%±7.1%(P<0.05)。50μmol/L GCDCA诱导p38及JNK磷酸化的作用[在p38为对照组的450.0%±12.2%(P<0.01),在JNK为对照组的210.0%±15.2%(P<0.05)]。50μmol/L GCDCA促进培养细胞的伤痕愈合(剩余面积为原来的75.4%±5.8%,P<0.05),而JNK(SP600125)或p38(SB294002)的抑制因子能够抑制胆汁酸的这种作用。结论胆汁酸具有促进肝星状细胞增殖的作用,还能提高该细胞的运动能力,这种作用是通过促进p38和JNK的磷酸化而实现的。提示胆汁酸可能通过调控p38和JNK的信号转导而促进肝纤维化的形成。

Objective Bile acids （BA） facilitate cholesterol hepatic fibrosis.Although hepatic stellate cell （HSC） is one of the most important cells during liver fibrogenesis,the effect of bile acids on HSC is rarely mentioned.Therefore,bile acids facilitate liver fibrosis through regulating activated HSC should be tested.Methods The amount of BrdU incorporation was determined to assess the proliferation of HSC treated by bile acid.Wound-healing assay was used to determine the cellular motility.Meanwhile,the phosphorylation of p38 and JNK in HSC was detected by Western blotting.Results 50 μmol /L GCDCA enhanced the HSC proliferation significantly （152.0% ± 7.1%,P〈 0.05）;50 μmol /L GCDCA also induced phosphorylation of p38 and JNK （450.0% ± 12.2% of control in p38 （P〈 0.01）,210.0% ± 15.2 % of control in JNK （P〈 0.05））.50 μmol /L GCDCA aided wound healing （remaining wound area is 75.4% ± 5.8% of original area,P〈 0.05）,but this effect was inhibited by JNK （SP600125） or p38 （SB294002） inhibitor,respectively.Conclusions Bile acids enhance HSC proliferation and facilitate cellular motility through inducing phosphorylation of p38 and JNK,indicating bile acid aid liver fibrosis through regulation of p38 and JNK signaling.