Long non‑coding RNA L13Rik promotes high glucose-induced mesangial cell hypertrophy and matrix protein expression by regulating miR-2861/CDKN1B axis

PeerJ. 2023 Oct 16:11:e16170. doi: 10.7717/peerj.16170. eCollection 2023.

Abstract

Background: Diabetic nephropathy (DN) is a frequent microvascular complication of diabetes. Glomerular mesangial cell (MC) hypertrophy occurs at the initial phase of DN and plays a critical role in the pathogenesis of DN. Given the role of long non coding RNA (lncRNA) in regulating MC hypertrophy and extracellular matrix (ECM) accumulation, our aim was to identify functional lncRNAs during MC hypertrophy.

Methods: Here, an lncRNA, C920021L13Rik (L13Rik for short), was identified to be up-regulated in DN progression. The expression of L13Rik in DN patients and diabetic mice was assessed using quantitative real-time PCR (qRT-PCR), and the function of L13Rik in regulating HG-induced MC hypertrophy and ECM accumulation was assessed through flow cytometry and western blotting analysis.

Results: The L13Rik levels were significantly increased while the miR-2861 levels were decreased in the peripheral blood of DN patients, the renal tissues of diabetic mice, and HG-treated MCs. Functionally, both L13Rik depletion and miR-2861 overexpression effectively reduced HG-induced cell hypertrophy and ECM accumulation. Mechanistically, L13Rik functioned as a competing endogenous RNA (ceRNA) to sponge miR-2861, resulting in the de-repression of cyclin-dependent kinase inhibitor 1B (CDKN1B), a gene known to regulate cell cycle and MC hypertrophy.

Conclusions: Collectively, the current results demonstrate that up-regulated L13Rik is correlated with DN and may be a hopeful therapeutic target for DN.

Keywords: CDKN1B; Diabetic nephropathy; L13Rik; Mesangial cell; miR-2861.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism
  • Diabetes Mellitus, Experimental* / genetics
  • Diabetic Nephropathies* / genetics
  • Glucose / pharmacology
  • Humans
  • Hypertrophy / genetics
  • Mesangial Cells / metabolism
  • Mice
  • MicroRNAs* / genetics
  • RNA, Long Noncoding* / genetics

Substances

  • RNA, Long Noncoding
  • MicroRNAs
  • Cyclin-Dependent Kinase Inhibitor p27
  • Glucose
  • CDKN1B protein, human
  • MIRN2861 microRNA, human
  • MIRN2861 microRNA, mouse

Grants and funding

This work was funded by the Natural Science Foundation of Shanghai (Grant Number 20ZR1451600) and the Shanghai Municipal Health Bureau Project (Grant Number 201940439). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.