Respective roles of the mitogen-activated protein kinase (MAPK) family members in pancreatic stellate cell activation induced by transforming growth factor-β1 (TGF-β1)
Respective roles of the mitogen-activated protein kinase (MAPK) family members in pancreatic stellate cell activation induced by transforming growth factor-β1 (TGF-β1)
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丝裂原激活蛋白激酶(MAPK)家族成员在转化生长因子-β1(TGF-β1)诱导的胰腺星状细胞活化中各自的作用
DOI：
10.1016/j.bbrc.2018.04.176
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发表时间：
2018-06-22
影响因子：
3.1
通讯作者：
Zhang, Hong
中科院分区：
文献类型：
--
作者：
Xu, Xiao-Fan;Liu, Fang;Zhang, Hong
活化的胰腺星状细胞（PSC）在胰腺纤维化的进展中起着至关重要的作用。转化生长因子-β（TGF-β）是诱导纤维化的最强刺激物之一。已知丝裂原活化蛋白激酶（MAPK）蛋白（包括ERK、JNK和p38 MAPK）有助于PSC活化和胰腺纤维化。已有研究证实TGF-β 1诱导的PSC活化与MAPK通路有关，但MAPK家族成员在PSC活化中的各自作用尚不清楚，哪个家族成员可能是小鼠PSC活化的关键介导因子仍存在争议。在这项研究中，我们研究了不同的MAPK家族成员（JNK，ERK和p38 MAPK）对小鼠PSC激活的影响，使用体内和体外模型。结果显示，CP组p-JNK、p-ERK和p-p38 MAPK均过表达，且p-JNK、p-ERK和p-p38 MAPK与活化的PSC共表达。在体外，TGF-β 1诱导PSC中JNK和ERK的过度表达。相反，PSC中p38 MAPK表达仅显示非常弱的增加。JNK和ERK特异性抑制剂抑制PSC中FN和α-SMA mRNA的表达，p38 MAPK抑制剂对PSC活化没有影响。这些结果表明，INK和ERK直接参与了TGE-beta 1诱导的PSC活化和胰腺纤维化的发展。p38 MAPK参与CP的发生、发展，但与TGF-β 1无直接反应，可能不是TGF-β 1激活PSC的靶点。(C)2018由Elsevier Inc.出版
Activated pancreatic stellate cells (PSCs) play a crucial role in the progression of pancreatic fibrosis. Transforming growth factor-beta (TGF-beta) is one of the strongest stimulator inducing fibrosis. The mitogenactivated protein kinase (MAPK) proteins (including ERK, JNK and p38 MAPK) are known to contribute to PSC activation and pancreatic fibrosis. Previous studies have identified PSC activation induced by TGF-beta 1 is related to MAPK pathway, but the respective role of MAPK family members in PSC activation still unclear, and which family member may be the key mediator in mice PSC activation still controversial. In this study, we investigated the influence of different MAPK family member (JNK, ERK, and p38 MAPK) on mice PSC activation using an in vivo and in vitro model. The results showed p-JNK, p-ERK and p-p38 MAPK were all over-expressed in CP group, and p-JNK, p-ERK, and p-p38 MAPK were co-expressed with activated PSC. In vitro, TGF-beta 1 induced JNK and ERK over-expression in PSCs. In contrast, p38 MAPK expression in PSC showed only a very weak increase. JNK- and ERK-specific inhibitors inhibited FN and alpha-SMA mRNA expression in PSCs, and a p38 MAPK inhibitor had no effect on PSC activation. These findings indicate that INK and ERK were directly involved in the PSCs activation induced by TGE-beta 1 and the development of pancreatic fibrosis. p38 MAPK participate in the progression of CP, but it does not respond to TGF-beta 1 directly and may not be regarded as the target of TGE-beta 1 induced PSC activation. (C) 2018 Published by Elsevier Inc.