1. lncRNA KCNQ1OT1 regulated high glucose-induced proliferation, oxidative stress, extracellular matrix accumulation, and inflammation by miR-147a/SOX6 in diabetic nephropathy (DN).
- Author
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Xu Y and Zhan X
- Subjects
- Cell Proliferation, Extracellular Matrix genetics, Extracellular Matrix metabolism, Extracellular Matrix pathology, Glucose metabolism, Glucose pharmacology, Humans, Inflammation genetics, Inflammation metabolism, Oxidative Stress, SOXD Transcription Factors metabolism, SOXD Transcription Factors pharmacology, Diabetes Mellitus metabolism, Diabetic Nephropathies genetics, Diabetic Nephropathies metabolism, MicroRNAs genetics, MicroRNAs metabolism, RNA, Long Noncoding genetics, RNA, Long Noncoding metabolism
- Abstract
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.
- Published
- 2022
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