Long noncoding RNA MALAT1 regulates renal tubular epithelial pyroptosis by modulated miR-23c targeting of ELAVL1 in diabetic nephropathy

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• 作者：Xue Li^a ; ^b ; ¹ ; ^{lixue5303@126.com} ; Li Zeng^a ; ¹ ; ^{aiyinsinian1986@163.com} ; Chuanwu Cao^a ; ^{18917683389@189.com} ; Chenhui Lu^a ; ^{lu_chenhui@163.com} ; Weishuai Lian^a ; ^{lianweishuai@126.com} ; Jianhong Han^a ; ^{hanjianh15@163.com} ; Xiaojun Zhang^a ; ^{zhangxiaojun2003@163.com} ; Jing Zhang^a ; ^{jjiangel2009@163.com} ; Tao Tang^a ; ^{tangtaotongji@163.com} ; Maoquan Li^a ; ^b ; ^{cjr.limaoquan@vip.163.com}
• 关键词：Long non-coding RNA ; MALAT1 ; MiR-23c ; Pyroptosis ; Diabetic nephropathy
• 刊名：Experimental Cell Research
• 出版年：2017
• 出版时间：15 January 2017
• 年：2017
• 卷：350
• 期：2
• 页码：327-335
• 全文大小：1311 K
• 卷排序：350

文摘

Diabetic nephropathy is a common kidney condition in patients with diabetes mellitus, which can result in renal failure. Pyroptosis, the process of pro-inflammatory programmed cell death, plays an important role in the pathogenesis of this disease. Long non-coding RNA MALAT1 has also been shown to be involved in diabetic nephropathy. Here, we investigated the role of MALAT1 and the microRNA miR-23c and its target gene ELAVL1 in renal tubular epithelial cells. Our data demonstrated that MALAT1 expression was substantially increased but miR-23c was decreased in streptozotocin-induced diabetic rats and in high-glucose-treated HK-2 cells. Downregulation of MALAT1 or upregulation the expression of miR-23c inhibited pyroptosis in HK-2 cells. In an effort to understand the signaling mechanisms underlying the pro-pyroptotic properties of MALAT1 and the anti-pyroptotic properties of miR-23c, we found that inhibiting the expression of MALAT1 downregulated the expression of ELAVL1, NLRP3, Caspase-1 and the pro-inflammatory cytokine IL-1β. These findings were replicated by upregulation of miR-23c. Moreover, luciferase assays showed that miR-23c, as a target of MALAT1, directly repressed ELAVL1 expression and then decreased the expression of its downstream protein NLRP3. The expression of MALAT1 antagonized the effect of miR-23c on the downregulation of its target ELAVL1 and inhibited hyperglycemia-induced cell pyroptosis. This mechanism may contribute to a better understanding of diabetic nephropathy pathogenesis and facilitate the development of new therapeutic strategies for the treatment of this disease.