Knockdown of TRIM27 expression suppresses the dysfunction of mesangial cells in lupus nephritis by FoxO1 pathway
Knockdown of TRIM27 expression suppresses the dysfunction of mesangial cells in lupus nephritis by FoxO1 pathway
复制标题
TRIM27表达敲低通过FoxO1通路抑制狼疮性肾炎肾小球系膜细胞功能障碍
DOI：
10.1002/jcp.27810
复制
发表时间：
2019-07-01
影响因子：
5.6
通讯作者：
Liu, Shuxia
中科院分区：
文献类型：
--
作者：
Liu, Jinxi;Feng, Xiaojuan;Liu, Shuxia
TRIM 27（tripartite motif-containing 27）是TRIM（tripartite motif-containing 27）蛋白家族的成员，参与多种生物学过程。有研究报道TRIM 27在某些肿瘤细胞和组织中高表达，在肿瘤细胞增殖中起重要作用。然而，TRIM 27是否参与狼疮性肾炎（LN）的进展，特别是细胞增殖仍不清楚。我们的研究表明，TRIM 27在LN患者的肾脏、狼疮小鼠和LN血浆暴露的系膜细胞中观察到过表达，其与系膜细胞的增殖和ECM（细胞外基质）沉积相关。TRIM 27表达下调通过调节FoxO 1通路抑制MRL/lpr小鼠和培养的人系膜细胞（HMCs）中的系膜细胞增殖和ECM积累。FoxO 1过表达可显著降低LN血浆处理的HMC增殖水平和ECM积累。此外，蛋白激酶B（Akt）信号通路抑制剂LY 294002可显著降低TRIM 27的表达，抑制系膜细胞功能障碍。提示TRIM 27介导了狼疮性肾炎肾小球系膜细胞的异常增殖，可能是治疗狼疮性肾炎肾小球系膜细胞增殖的潜在靶点。
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.