lncRNA KCNQ1OT1 regulated high glucose-induced proliferation, oxidative stress, extracellular matrix accumulation, and inflammation by miR-147a/SOX6 in diabetic nephropathy (DN)

[摘要] Long non-coding RNAs (lncRNAs) have been proved to play critical roles in diabetic nephropathy (DN). This study aimed to investigate the functions and underlying mechanism of potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (KCNQ1OT1) in DN. Blood samples were obtained from 33 DN patients and 30 healthy volunteers. Kidney biopsies tissues of DN patients (n = 10) and patients with normal kidney morphology (n = 10) were collected. We found that KCNQ1OT1 was markedly overexpressed in the blood and kidney biopsies tissues of DN patients, as well as in high glucose (HG)-cultured human glomerular mesangial (HGMC) cells. Knockdown of KCNQ1OT1 suppressed proliferation, extracellular matrix (ECM) accumulation, inflammation, and oxidative stress in HG-treated HGMC cells in vitro. KCNQ1OT1 functioned as a sponge for microRNA-147a (miR-147a), and SRY-Box Transcription Factor 6 (SOX6) was directly targeted by miR-147a. Downregulation of miR-147a or upregulation of SOX6 partly overturned the prohibitive effects of KCNQ1OT1 knockdown or miR-147a overexpression on proliferation, ECM accumulation, inflammation, and oxidative stress in HG-treated HGMC cells. Altogether, KCNQ1OT1 mediated the proliferation, ECM accumulation, inflammation, and oxidative stress in HG-treated HGMC cells via miR-147a/SOX6 axis, which might be a novel target for DN therapy.

[学科分类] 内分泌与代谢学

[关键词] Long non-coding RNAs (lncRNAs);KCNQ1OT1;miR-147a;SOX6;Diabetic nephropathy