title: 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.affiliation: Department of Interventional & Vascular Surgery, Tenth People's Hospital of Tongji University, No 301 Middle Yan Chang Road, Shanghai 200072, China; Institute of Interventional & Vascular Surgery, Tongji University, No 301 Middle Yan Chang Road, Shanghai 200072, China. Electronic address: lixue5303@126.com.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Interventional & Vascular Surgery, Tenth People's Hospital of Tongji University, No 301 Middle Yan Chang Road, Shanghai 200072, China. Electronic address: aiyinsinian1986@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Interventional & Vascular Surgery, Tenth People's Hospital of Tongji University, No 301 Middle Yan Chang Road, Shanghai 200072, China. Electronic address: 18917683389@189.com.
authors.forename: Chuanwu
authors.initials: C
authors.lastname: Cao
authors.affiliation: Department of Interventional & Vascular Surgery, Tenth People's Hospital of Tongji University, No 301 Middle Yan Chang Road, Shanghai 200072, China. Electronic address: lu_chenhui@163.com.
authors.forename: Chenhui
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Interventional & Vascular Surgery, Tenth People's Hospital of Tongji University, No 301 Middle Yan Chang Road, Shanghai 200072, China. Electronic address: lianweishuai@126.com.
authors.forename: Weishuai
authors.initials: W
authors.lastname: Lian
authors.affiliation: Department of Interventional & Vascular Surgery, Tenth People's Hospital of Tongji University, No 301 Middle Yan Chang Road, Shanghai 200072, China. Electronic address: hanjianh15@163.com.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Interventional & Vascular Surgery, Tenth People's Hospital of Tongji University, No 301 Middle Yan Chang Road, Shanghai 200072, China. Electronic address: zhangxiaojun2003@163.com.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Interventional & Vascular Surgery, Tenth People's Hospital of Tongji University, No 301 Middle Yan Chang Road, Shanghai 200072, China. Electronic address: jjiangel2009@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Interventional & Vascular Surgery, Tenth People's Hospital of Tongji University, No 301 Middle Yan Chang Road, Shanghai 200072, China. Electronic address: tangtaotongji@163.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Tang
authors.affiliation: Department of Interventional & Vascular Surgery, Tenth People's Hospital of Tongji University, No 301 Middle Yan Chang Road, Shanghai 200072, China; Institute of Interventional & Vascular Surgery, Tongji University, No 301 Middle Yan Chang Road, Shanghai 200072, China. Electronic address: cjr.limaoquan@vip.163.com.
authors.forename: Maoquan
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000067780:ELAV-Like Protein 1 / Q000235:genetics* / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics / Q000378:metabolism; D000069292:Pyroptosis; D062085:RNA, Long Noncoding / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000067780:ELAV-Like Protein 1; D053583:Interleukin-1beta; C000598685:MALAT1 long noncoding RNA, rat; D035683:MicroRNAs; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D062085:RNA, Long Noncoding; C546082:mirn21 microRNA, rat; D020170:Caspase 1
keywords: Diabetic nephropathy; Long non-coding RNA; MALAT1; MiR-23c; Pyroptosis