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Knockdown of TRIM27 expression suppresses the dysfunction of mesangial cells in lupus nephritis by FoxO1 pathway
Author(s) -
Liu Jinxi,
Feng Xiaojuan,
Tian Yu,
Wang Kexin,
Gao Fan,
Yang Lin,
Li Hongbo,
Tian Yuexin,
Yang Ran,
Zhao lu,
Miao Xinyan,
Huang Jie,
Liu Qingjuan,
Zhang Wei,
Li Yuzhe,
Wang Chunlin,
Duan Huijun,
Liu Shuxia
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27810
Subject(s) - mesangial cell , cell growth , downregulation and upregulation , gene knockdown , lupus nephritis , signal transduction , microbiology and biotechnology , extracellular matrix , biology , protein kinase b , pi3k/akt/mtor pathway , cancer research , cell culture , chemistry , endocrinology , medicine , kidney , biochemistry , genetics , disease , gene
Abstract TRIM27 (tripartite motif‐containing 27) is a member of the TRIM (tripartite motif) protein family and participates in a variety of biological processes. Some research has reported that TRIM27 was highly expressed in certain kinds of carcinoma cells and tissues and played an important role in the proliferation of carcinoma cells. However, whether TRIM27 takes part in the progression of lupus nephritis (LN) especially in cells proliferation remains unclear. Our study revealed that the overexpression of TRIM27 was observed in the kidneys of patients with LN, lupus mice and mesangial cells exposed to LN plasma which correlated with the proliferation of mesangial cells and ECM (extracellular matrix) deposition. Downregulation of TRIM27 expression suppressed the proliferation of mesangial cells and ECM accumulation in MRL/lpr mice and cultured human mesangial cells (HMCs) by regulating the FoxO1 pathway. Furthermore, the overexpression of FoxO1 remarkably decreased HMCs proliferation level and ECM accumulation in LN plasma‐treated HMCs. In addition, the protein kinase B (Akt) signal pathway inhibitor LY294002 significantly reduced the expression of TRIM27 and inhibited the dysfunction of mesangial cells. These above data suggested that TRIM27 mediated abnormal mesangial cell proliferation in kidney of lupus and might be the potential target for treating mesangial cell proliferation of lupus nephritis.