LncRNA Dlx6os1 Accelerates Diabetic Nephropathy Progression by Epigenetically Repressing SOX6 via Recruiting EZH2
Yan-Xia Chen1, Shu-Ying Zhu1, Chong Huang1
1Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Introduction:
Diabetic nephropathy (DN) is the leading cause of kidney failure worldwide. To explore the pathogenesis and effective biological target of DN is beneficial to seeking novel treatment strategies.
Objective:
This study aimed to investigate the role of the lncRNA Dlx6os1/SOX6/EZH2 axis in DN progression.
Methods:
PAS staining was performed to evaluate extracellular matrix accumulation; ELISA was carried out to assess the levels of urine microalbumin and blood glucose concentration; RT-qPCR was carried out to detect the levels of lncRNA Dlx6os1, TNF-α, IL-1β, IL-6, SOX6, and EZH2. Western blot was performed to assess the levels of Col-IV, FN, TGF-β1, and SOX6 proteins. RIP assay was carried out to verify the interaction between lncRNA Dlx6os1 and EZH2. ChIP-qPCR was conducted to verify the interaction between EZH2 and SOX6 promoter.
Results:
Our results illustrated that lncRNA Dlx6os1 was highly expressed in DN mice and HG-induced SV40 MES13 cells. LncRNA Dlx6os1 knockdown inhibited HG-induced SV40 MES13 cell proliferation, fibrosis, and inflammatory cytokine release. LncRNA Dlx6os1 inhibited SOX6 expression by recruiting EZH2 in HG-SV40 MES13 cells, and SOX6 mediated the effects of lncRNA Dlx6os1 on proliferation, fibrosis, and inflammatory factor release of HG-induced SV40 MES13 cells.
Conclusion:
LncRNA Dlx6os1 accelerates the progression of DN by epigenetically repressing SOX6 via recruiting EZH2.
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