Long non-coding RNA HCG18 promotes M1 macrophage polarization through regulating the miR-146a/TRAF6 axis, facilitating t
- PDF / 3,156,247 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 102 Downloads / 161 Views
Long non‑coding RNA HCG18 promotes M1 macrophage polarization through regulating the miR‑146a/TRAF6 axis, facilitating the progression of diabetic peripheral neuropathy Wei Ren1 · Guangxia Xi1 · Xing Li2 · Lingxia Zhao1 · Kun Yang1 · Xuemei Fan1 · Linlin Gao1 · Hongmei Xu1 · Jianjin Guo2 Received: 3 June 2020 / Accepted: 19 September 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Diabetic peripheral neuropathy (DPN) is one of the most important complications in diabetes mellitus (DM), which has been reported to be modulated by long non-coding RNAs (lncRNAs). The purpose of the current study is to explore the regulatory mechanism of lncRNA HCG18 on DPN in vitro. The expression of lncRNA HCG18, miR-146a, TRAF6, CD11c, and iNOS was detected by qRT-PCR. Through Enzyme-linked immunosorbent assay, the levels of inflammatory factors (TNF-α, IL-1β, and IL-6) were determined. M1 macrophage polarization was measured by flow cytometry analysis. The interactions between miR-146a and HCG18/TRAF6 were predicted by Starbase/Targetscan software and verified by the dual luciferase reporter assay. Western blot assay was performed to determine the protein expression of TRAF6. LncRNA HCG18 was highly expressed in DPN model and HG-induced macrophages. The levels of inflammatory factors (TNF-α, IL-1β, and IL-6) were elevated in DPN model. The expression of M1 markers (CD11c and iNOS) was visibly up-regulated in DPN model and was positively correlated with HCG18 expression. LncRNA HCG18 facilitated M1 macrophage polarization. In addition, miR146a was identified as a target of lncRNA HCG18. Overexpression of miR-146a reversed the promoting effect of HCG18 on M1 macrophage polarization. Simultaneously, TRAF6 was a target gene of miR-146a TRAF6 expression was positively modulated by HCG18 and was negatively modulated by miR-146a. Down-regulation of TRAF6 reversed the promoting effect of HCG18 on M1 macrophage polarization. LncRNA HCG18 promotes M1 macrophage polarization via regulating the miR-146a/TRAF6 axis, facilitating the progression of DPN. This study provides a possible therapeutic strategy for DPN. Keywords Diabetic peripheral neuropathy · lncRNA HCG18 · miR-146a · TRAF6 · Macrophage polarization
Introduction Diabetes mellitus (DM) has become an epidemic problem in the twenty-first century [1]. According to the International Diabetes Federation, the global population of diabetes patients is predicted to reach a pandemic level of 366 * Jianjin Guo [email protected] 1
Department of Endocrinology and Metabolism, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, No. 99, Longcheng Street, Taiyuan City 030032, Shanxi Province, China
Department of Endocrinology and Metabolism, The Second Clinical Medical College of Shanxi Medical University, The Second Hospital of Shanxi Medical University, No. 382, WuYi Road, Taiyuan City 030001, Shanxi Province, China
2
million by 2030, double the number from 2000 [1]. Diabetic peripheral neuropathy (DPN) is the main complication of type 2
Data Loading...
