RNF2 Mediates Hepatic Stellate Cells Activation by Regulating ERK/p38 Signaling Pathway in LX-2 Cells.
RNF2 Mediates Hepatic Stellate Cells Activation by Regulating ERK/p38 Signaling Pathway in LX-2 Cells.
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RNF2 通过调节 LX-2 细胞中的 ERK/p38 信号通路介导肝星状细胞激活
DOI：
10.3389/fcell.2021.634902
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发表时间：
2021
影响因子：
5.5
通讯作者：
Du J
中科院分区：
文献类型：
--
作者：
Yan Q;Pan L;Qi S;Liu F;Wang Z;Qian C;Chen L;Du J
肝纤维化的治疗方法仍是世界范围内尚未解决的临床难题。值得注意的是，细胞外基质（ECM）在肝脏中的积累是由细胞因子和生长因子如肝星状细胞（HSC）中的转化生长因子-β1（TGF-β1）的产生介导的。环指蛋白2（Ring finger protein 2，RNF 2）是多梳抑制复合物1（polycomb repressive complex 1，PRC 1）的催化亚基，介导组蛋白H2 A的单泛素化。近年来，越来越多的证据表明RNF 2可能在癌症的多种病理过程中发挥重要作用。在此，我们探讨了RNF 2在肝纤维化中的作用及其潜在机制。结果表明，RNF 2在人肝纤维化组织中表达上调。RNF 2基因敲低导致LX-2细胞中胶原1和α-平滑肌肌动蛋白（α-SMA）的表达下降，而RNF 2基因过表达则上调胶原1和α-SMA的表达。RNF 2过表达可显著促进TGF-β1诱导的LX-2细胞增殖，但抑制凋亡。此外，RNF 2的敲低抑制了由TGF-β1诱导的ERK/p38信号通路的激活。这些数据表明，RNF 2是通过ERK/p38信号通路激活HSC的有效促纤维化因子。RNF 2抑制可能是肝纤维化的一个有前途的治疗靶点。
The therapeutic approach of liver fibrosis is still an unsolved clinical problem worldwide. Notably, the accumulation of extracellular matrix (ECM) in the liver is mediated by the production of cytokines and growth factors, such as transforming growth factor-β1 (TGF-β1) in hepatic stellate cells (HSCs). Ring finger protein 2 (RNF2) was identified as the catalytic subunit of polycomb repressive complex 1 (PRC1), mediating the monoubiquitination of histone H2A. In recent years, a growing amount of evidence suggests that RNF2 may play an important role in multiple pathological processes involved in cancer. Here, we explored the role of RNF2 in liver fibrogenesis and its potential mechanisms. The results showed that RNF2 was up-regulated in human fibrotic liver tissue. Knockdown of RNF2 led to a decreasing expression of collagen1 and α-smooth muscle actin (α-SMA) in LX-2 cells, which was upregulated by RNF2 overexpression. Moreover, RNF2 overexpression significantly promoted TGF-β1-induced LX-2 cell proliferation but decreased apoptosis. Furthermore, knockdown of RNF2 inhibited the activation of ERK/p38 signaling pathways induced by TGF-β1. These data suggested that RNF2 is an effective pro-fibrogenic factor for HSC activation via ERK/p38 signaling pathway. RNF2 inhibition might be a promising therapeutic target for liver fibrosis.
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影响因子：
3.4
作者：
Rao, Prema S.;Satelli, Arun;Zhang, Sheng;Srivastava, Sanjay K.;Srivenugopal, Kalkunte S.;Rao, U. Subrahmanyeswara
通讯作者：
Rao, U. Subrahmanyeswara
肝纤维化中细胞外基质的细胞来源。
影响因子：
5.1
作者：
Wells RG
通讯作者：
Wells RG
影响因子：
3.6
作者：
Castilho-Fernandes, Andrielle;de Almeida, Danilo Candido;Covas, Dimas Tadeu
通讯作者：
Covas, Dimas Tadeu
DOI：
10.1016/j.bbrc.2018.05.081
发表时间：
2018-07-02
影响因子：
3.1
作者：
Yang, Jianyu;Zhang, Naiwen;Kong, Chuize
通讯作者：
Kong, Chuize
影响因子：
4.8
作者：
He, Yong;Huang, Cheng;Li, Jun
通讯作者：
Li, Jun