CircTAOK1 regulates high glucose induced inflammation, oxidative stress, ECM accumulation, and apoptosis in diabetic nephropathy via targeting miR‐142‐3p/SOX6 axis

Abstract

AbstractBackgroundDiabetic nephropathy (DN) is a complication caused by diabetes. Circular RNAs (circRNAs) are a kind of RNA with a closed circular structure, which has high stability and is involved in many disease‐related processes. The mechanism of circRNA TAO kinase 1 (circTAOK1) in the pathogenesis and development of DN is unclear.MethodsCircTAOK1, microRNA (miR)‐142‐3p, and sex‐determining region Y‐box transcription factor 6 (SOX6) mRNA levels were analyzed by real‐time quantitative polymerase chain reaction (RT‐qPCR). Cell counting kit‐8 (CCK8) and 5‐ethynyl‐2′‐deoxyuridine (EdU) assays were used to analyze cell proliferation. Cell cycle distribution was detected by flow cytometry. Western blot assay was performed to test B‐cell lymphoma 2 (Bcl‐2), Bcl‐2 associated X (Bax), cleaved‐caspase 3, and fibronectin (FN), collagen I (Col I), and collagen IV (Col IV) protein levels. ELISA assay was used to measure interleukin 1β (IL‐1β), interleukin 6 (IL‐6), and tumor necrosis factor (TNF‐α) levels. The reactive oxygen species (ROS) and malondialdehyde (MDA) levels and the superoxide dismutase (SOD) activity were assessed by the corresponding kits. And the correlation between miR‐142‐3p and circTAOK1 or SOX6 was confirmed by dual luciferase reporter assay, RNA immunoprecipitation assay and RNA pull down assay.ResultsCircTAOK1 and SOX6 expression levels were up‐regulated, while miR‐142‐3p expression was down‐regulated in DN serum and HG‐treated HK‐2 cells. Knockdown of circTAOK1 could inhibit cell injury of HG‐induced HK‐2 cells. The inhibitory effect of circTAOK1 knockdown on HG‐induced HK‐2 cell injury was restored by miR‐142‐3p downregulation. CircTAOK1 acted as a sponge for miR‐142‐3p, and SOX6 was targeted by miR‐142‐3p. The overexpression of SOX6 could recover the effect of miR‐142‐3p overexpression on HG‐induced HK‐2 cell injury. CircTAOK1 regulated the expression of SOX6 by targeting miR‐142‐3p.ConclusionCircTAOK1 knockdown inhibited HG‐induced HK‐2 cell damage in DN by the miR‐142‐3p/SOX6 axis.