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

Abstract

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.

• Authors: Xue Li, Li Zeng, Chuanwu Cao, Chenhui Lu, Weishuai Lian, Jianhong Han, Xiaojun Zhang, Jing Zhang, Tao Tang, Maoquan Li
• Journal: Experimental cell research (Exp Cell Res) Vol. 350 Issue 2 Pg. 327-335 (Jan 15 2017) ISSN: 1090-2422 [Electronic] United States
• PMID: 27964927 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• ELAV-Like Protein 1
• Interleukin-1beta
• MALAT1 long noncoding RNA, rat
• MicroRNAs
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, rat
• RNA, Long Noncoding
• mirn21 microRNA, rat
• Caspase 1

Topics

• Animals
• Caspase 1 (genetics, metabolism)
• Cell Line
• Diabetic Nephropathies (genetics, metabolism, pathology)
• ELAV-Like Protein 1 (genetics, metabolism)
• Epithelial Cells (metabolism)
• Humans
• Interleukin-1beta (genetics, metabolism)
• Kidney Tubules (cytology, metabolism)
• MicroRNAs (genetics)
• NLR Family, Pyrin Domain-Containing 3 Protein (genetics, metabolism)
• Pyroptosis
• RNA, Long Noncoding (genetics)
• Rats
• Rats, Sprague-Dawley