"Long non-coding RNA CASC2 restrains high glucose-induced proliferation, inflammation and fibrosis in human glomerular mesangial cells through mediating miR-135a-5p/TIMP3 axis and JNK signaling"

作者全名："Zhu, Dongju; Wu, Xiang; Xue, Qian"

作者地址："[Zhu, Dongju] Panzhihua Univ, Dept Nephrol, Affiliated Hosp, Panzhihua 617000, Sichuan, Peoples R China; [Wu, Xiang] Panzhihua Cent Hosp, Dept Pediat, Panzhihua 617000, Sichuan, Peoples R China; [Xue, Qian] Chongqing Med Univ, Dept Gastroenterol, Affiliated Hosp 1, Chongqing 400000, Peoples R China"

通信作者："Zhu, DJ (corresponding author), Panzhihua Univ, Dept Nephrol, Affiliated Hosp, Panzhihua 617000, Sichuan, Peoples R China."

来源：DIABETOLOGY & METABOLIC SYNDROME

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000690989600001

JCR分区：Q2

影响因子：4.8

年份：2021

卷号：13

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Diabetic nephropathy; High glucose; CASC2; miR-135a-5p; TIMP3

摘要："Background: Diabetic nephropathy (DN) is a common complication of diabetes. Long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) is reported to exert a protective role in DN by a previous study. The working mechanism underlying the protective role of CASC2 in DN progression was further explored in this study. Methods: The expression of CASC2 and microRNA-135a-5p (miR-135a-5p) was determined by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation ability was assessed by Cell Counting Kit-8 (CCK8) assay and 5-ethynyl-29-deoxyuridine (EDU) assay. Enzyme-linked immunosorbent assay (ELISA) was conducted to analyze the production of inflammatory cytokines in the supernatant. Western blot assay was performed to analyze protein expression. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to verify the target relationship between miR-135a-5p and CASC2 or tissue inhibitors of metalloproteinase 3 ( TIMP3). Results: High glucose (HG) treatment reduced the expression of CASC2 in human glomerular mesangial cells (HMCs) in a time-dependent manner. CASC2 overexpression suppressed HG-induced proliferation, inflammation and fibrosis in HMCs. miR-135a-5p was validated as a target of CASC2, and CASC2 restrained HG-induced influences in HMCs partly by down-regulating miR-135a-5p. miR-135a-5p bound to the 3' untranslated region (3'UTR) of TIMP3, and CASC2 positively regulated TIMP3 expression by sponging miR-135a-5p in HMCs. miR-135a-5p silencing inhibited HG-induced effects in HMCs partly by up-regulating its target TIMP3. CASC2 overexpression suppressed HG-induced activation of Jun N-terminal Kinase (JNK) signaling partly through mediating miR-135a-5p/TIMP3 signaling. Conclusions: In conclusion, CASC2 alleviated proliferation, inflammation and fibrosis in DN cell model by sponging miR-135a-5p to induce TIMP3 expression."

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