MicroRNA (miR)-590-3p alleviates high-glucose induced renal tubular epithelial cell damage by targeting C-X3-C motif chemokine ligand 1 (CX3CL1) in diabetic nephropathy

Bioengineered. 2022 Jan;13(1):634-644. doi: 10.1080/21655979.2021.2012548.

Abstract

We attempted to analyze the clinical value of microRNA (miR)-590-3p in diabetic nephropathy (DN) patients and its role in high glucose (HG)-induced renal tubular epithelial cell (HK-2) injury. Serum levels of miR-590-3p were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Spearman correlation coefficient analysis of the correlation between miR-590-3p and clinical indicators. The diagnostic value of miR-590-3p was analyzed by the receiver operating characteristic (ROC) curve. Then, the DN cell model induced by HG in HK-2 cells was established. Enzyme-linked immunosorbent assay (ELISA), flow cytometry, and CCK-8 assay were employed to assess cell inflammation, oxidative stress, apoptosis, and proliferation. Dual-luciferase reporter assay confirmed the target of miR-590-3p. Serum miR-590-3p was reduced in patients of DN, which was positively correlated with eGFR and negatively associated with albuminuria. Furthermore, miR-590-3p also can diagnose patients of DN from healthy subjects or patients of T2DM. Furthermore, miR-590-3p was decreased in a concentration- and time-dependent manner during HG-induction. miR-590-3p overexpression bated HG-induced inhibition effect on cell proliferation and promotion effects on apoptosis, oxidative stress, and inflammation. C-X3-C motif chemokine ligand1 (CX3CL1) is the target of miR-590-3p, whose levels were enhanced in DN patients and are negatively regulated by miR-590-3p. Our discoveries offered new insights that reduced miR-590-3p as a potential biomarker for the diagnosis of DN, and elevated miR-590-3p can alleviate renal tubular injury by HG-induced through targeting CX3XL1, which may be a novel target for improving the development of DN.

Keywords: Mir-590-3p; diabetic nephropathy; renal tubule injury.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Adult
  • Aged
  • Cell Line
  • Chemokine CX3CL1 / metabolism*
  • Diabetic Nephropathies / metabolism*
  • Epithelial Cells / metabolism*
  • Female
  • Glucose / metabolism*
  • Humans
  • Kidney Tubules / metabolism*
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged

Substances

  • CX3CL1 protein, human
  • Chemokine CX3CL1
  • MIRN590 microRNA, human
  • MicroRNAs
  • Glucose

Grants and funding

This study was funded by the National Natural Science Foundation of China(Grant number 81804088); Construction Program of National TCM Clinical Research Base(Grant number JDZX2015192); University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province(Grant number UPYSCT-2018222); Heilongjiang Postdoctoral Fund(Grant number LBH-Z15210); Natural Science Foundation of Heilongjiang Province of China (Grant number H2016078); Research Foundation of Heilongjiang University of Chinese Medicine (Grant number 2015bs01).