Long non-coding RNA CDKN2B-AS1 regulates high glucose-induced human mesangial cell injury via regulating the miR-15b-5p/
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Diabetology & Metabolic Syndrome Open Access
RESEARCH
Long non‑coding RNA CDKN2B‑AS1 regulates high glucose‑induced human mesangial cell injury via regulating the miR‑15b‑5p/WNT2B axis Jing Chang1†, Yanming Yu2†, Zhan Fang1, Haiyan He1, Dan Wang1, Jian Teng1 and Lina Yang2*
Abstract Background: Long non-coding RNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) has been reported to be related to diabetic nephropathy (DN) progression. However, the regulatory mechanisms of CDKN2BAS1 in DN are unclear. Methods: High glucose (HG) was used to induce human mesangial cells (HMCs) for establishing the DN model. Expression levels of CDKN2B-AS1, microRNA (miR)-15b-5p, wingless-Type family member 2B (WNT2B) mRNA in serum and HMCs were detected through quantitative real-time polymerase chain reaction (qRT-PCR). The viability and cell cycle progression of HMCs were determined with Cell Counting Kit-8 (CCK-8) or flow cytometry assays. The levels of several proteins and inflammatory factors in HMCs were analyzed by western blotting or enzyme-linked immunosorbent assay (ELISA). The relationship between CDKN2B-AS1 or WNT2B and miR-15b-5p was verified with dualluciferase reporter assay. Results: CDKN2B-AS1 and WNT2B were upregulated while miR-15b-5p was downregulated in serum of DN patients and HG-treated HMCs. CDKN2B-AS1 inhibition reduced HG-induced viability, cell cycle progression, ECM accumulation, and inflammation response in HMCs. CDKN2B-AS1 regulated WNT2B expression via competitively binding to miR-15b-5p. MiR-15b-5p inhibitor reversed CDKN2B-AS1 knockdown-mediated influence on viability, cell cycle progression, ECM accumulation, and inflammation response of HG-treated HMCs. The repressive effect of miR-15b-5p mimic on viability, cell cycle progression, ECM accumulation, and inflammation response of HG-treated HMCs was abolished by WNT2B overexpression. Conclusion: CDKN2B-AS1 regulated HG-induced HMC viability, cell cycle progression, ECM accumulation, and inflammation response via regulating the miR-15b-5p/WNT2B axis, provided a new mechanism for understanding the development of DN. Keywords: DN, CDKN2B-AS1, miR-15b-5p, WNT2B
*Correspondence: [email protected] † Jing Chang and Yanming Yu contributed equally to this work 2 Department of Nephrology, Yantai Yuhuangding Hospital, No. 20 Yuhuangding East Road, Yantai 264000, Shandong, China Full list of author information is available at the end of the article
Introduction Diabetic nephropathy (DN) is a common cause of end-stage renal disease [1]. DN is characterized by mesangial hypertrophy, which is caused by mesangial cell proliferation and excessive accumulation of extracellular matrix (ECM) [2, 3]. Also, about 20–50% of people with diabetes will develop DN [4]. At present,
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