Department of Pediatric, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province 524001, China.
VIP Inpatient Area, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong Province, 524001, China.
Exp Mol Pathol. 2020 Jun;114:104384. doi: 10.1016/j.yexmp.2020.104384. Epub 2020 Jan 24.
Lupus nephritis (LN) is a chronic autoimmune disease. Recently, microRNA (miR)-133 has been demonstrated to play an important role in renal cell carcinoma. Our current study was designed to test the role of miR-133 and its potential target in LN. First, significant correlation of LASP1 and miR-133 levels was observed in the human LN tissue. Modification of miR-133 level in the human mesangial cells (HMCs) by either overexpression or knockdown demonstrated a suppressive role of miR-133 in cell proliferation and an inductive role in cell apoptosis. Modification of LASP1 level in the HMCs demonstrated the opposing effects of LASP1 to miR-133 on proliferation and apoptosis. In addition, luciferase assay showed miR-133 directly regulates LASP1 expression through its binding site in the 3'UTR of LASP1. At last, our data showed that the changes in properties, such as suppression in proliferation and induction in apoptosis, induced by overexpression of miR-133 were restored by additional expression of LASP1. In summary, our obtained data demonstrated that miR-133 suppresses proliferation and promotes apoptosis through its binding with LASP1 in human mesangial cells. This study revealed a new mechanism involving the interaction of miR-133 and LASP1 in the pathogenesis of LN.
狼疮性肾炎（LN）是一种慢性自身免疫性疾病。最近，microRNA（miR）-133 已被证明在肾细胞癌中发挥重要作用。我们的研究旨在测试 miR-133 及其在 LN 中的潜在靶标在疾病中的作用。首先，我们在人 LN 组织中观察到 LASP1 和 miR-133 水平之间存在显著相关性。通过过表达或敲低 miR-133 来调节人肾小球系膜细胞（HMCs）中的 miR-133 水平，结果表明 miR-133 抑制细胞增殖，诱导细胞凋亡。调节 HMCs 中的 LASP1 水平则表明 LASP1 与 miR-133 对增殖和凋亡具有相反的作用。此外，荧光素酶报告基因实验表明 miR-133 通过其在 LASP1 3'UTR 中的结合位点直接调节 LASP1 的表达。最后，我们的数据表明，过表达 miR-133 诱导的增殖抑制和凋亡诱导等特性变化可通过 LASP1 的额外表达得到恢复。综上所述，我们的数据表明 miR-133 通过与 LASP1 结合抑制人肾小球系膜细胞的增殖并促进凋亡。本研究揭示了 miR-133 和 LASP1 在 LN 发病机制中相互作用的新机制。
