Suppressors of Cytokine Signaling Inhibit Tubular Epithelial Cell-Myofibroblast Transdifferentiation
Suppressors of Cytokine Signaling Inhibit Tubular Epithelial Cell-Myofibroblast Transdifferentiation
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细胞因子信号传导抑制剂抑制管状上皮细胞-肌成纤维细胞转分化
DOI：
10.1159/000329325
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发表时间：
2011-07
影响因子：
4.2
通讯作者：
Duan, Huijun
中科院分区：
文献类型：
--
作者：
Liu, Qingjuan;Liu, Shuxia;Shi, Yonghong;Li, Hang;Hao, Jun;Xing, Lingling;Cao, Yanping;Duan, Huijun
背景/目的：管状上皮细胞-肌成纤维细胞转分化（TEMT）可以由多种细胞因子诱导。细胞因子信号传导抑制蛋白 (SOCS) 蛋白负向调节细胞因子信号传导。本研究旨在探讨SOCS-1和SOCS-3在细胞因子诱导的TEMT中的作用。方法：采用透射电镜观察细胞超微结构。采用免疫细胞化学、Western blot和实时PCR检测细胞角蛋白18（CK18）和α-平滑肌肌动蛋白（α-SMA）的蛋白和mRNA水平。通过Western blot检测磷酸化信号转导子和转录激活子(p-STAT)1和3的水平。通过Western blot和实时PCR检测SOCS-1和SOCS-3的蛋白和mRNA水平。通过 ELISA 测定 I 型胶原蛋白和纤连蛋白 (FN) 的水平。结果：在培养的人肾近端肾小管上皮细胞 (HKC) 中，白细胞介素 1β (IL-1β) 和制瘤素 M (OSM) 能够下调 CK18 表达并上调 α-SMA、p-STAT1、p-STAT3、I 型胶原和 FN 表达，而 AG490 预处理可防止这些表达变化的发生。 IL-1β或OSM诱导的所有变化均可因SOCS-1和SOCS-3过表达而减少，并因SOCS-1和SOCS-3敲低而增加。结论：SOCS-1和SOCS-3可以通过抑制TEMT来预防肾小管间质纤维化，其机制可能与STAT1和STAT3的激活有关。
Background/Aims: Tubular epithelial cell-myofibroblast transdifferentiation (TEMT) can be induced by diverse cytokines. The suppressors of cytokine signaling (SOCS) proteins negatively regulate cytokine signaling. This study is aimed at examining the role of SOCS-1 and SOCS-3 in TEMT induced by cytokines. Methods: The cell ultrastructure was observed using transmission electron microscopy. The protein and mRNA levels of cytokeratin 18 (CK18) and α-smooth muscle actin (α-SMA) were detected by immunocytochemistry, Western blot and real-time PCR. The levels of phosphorylated-signal transducer and activator of transcription (p-STAT) 1 and 3 were detected by Western blot. The protein and mRNA levels of SOCS-1 and SOCS-3 were detected by Western blot and real-time PCR. The levels of collagen type I and fibronectin (FN) were determined by ELISA. Results: Interleukin-1β (IL-1β) and oncostatin M (OSM) were able to downregulate CK18 expression and upregulate α-SMA, p-STAT1, p-STAT3, collagen type I and FN expression in cultured human renal proximal tubular epithelial cells (HKCs), whereas pretreatment with AG490 prevented these expression changes from occurring. All of the changes induced by IL-1β or OSM could be decreased by SOCS-1 and SOCS-3 overexpression, and were increased by SOCS-1 and SOCS-3 knockdown. Conclusions: SOCS-1 and SOCS-3 can prevent tubulointerstitial fibrosis by inhibiting TEMT, which may be connected with the activation of STAT1 and STAT3.
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影响因子：
3.8
作者：
Jong-In Park;C. Strock;D. Ball;B. Nelkin
通讯作者：
Jong-In Park;C. Strock;D. Ball;B. Nelkin
影响因子：
19.6
作者：
Ng, YY;Huang, TP;Lan, HY
通讯作者：
Lan, HY
DOI：
10.1097/01.asn.0000102479.92582.43
发表时间：
2004-01-01
影响因子：
13.6
作者：
Nightingale, J;Patel, S;Zhang, Z
通讯作者：
Zhang, Z
影响因子：
19.6
作者：
Rastaldi, MP;Ferrario, F;D'Amico, G
通讯作者：
D'Amico, G
影响因子：
--
作者：
Christian Schindler;I. Strehlow
通讯作者：
Christian Schindler;I. Strehlow