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LncRNA TUG1/miR-29c-3p/SIRT1 axis regulates endoplasmic reticulum stress-mediated renal epithelial cells injury in diabetic nephropathy model in vitro.

Abstract
Long non-coding RNAs (lncRNAs) are important regulators in diabetic nephropathy. In this study, we investigated the potential role of lncRNA TUG1 in regulating endoplasmic reticulum stress (ERS)-mediated apoptosis in high glucose induced renal tubular epithelial cells. Human renal tubular epithelial cell line HK-2 was challenged with high glucose following transfection with lncRNA TUG1, miR-29c-3p mimics or inhibitor expression plasmid, either alone or in combination, for different experimental purposes. Potential binding effects between TUG1 and miR-29c-3p, as well as between miR-29c-3p and SIRT1 were verified. High glucose induced apoptosis and ERS in HK-2 cells, and significantly decreased TUG1 expression. Overexpressed TUG1 could prevent high glucose-induced apoptosis and alleviated ERS via negatively regulating miR-29c-3p. In contrast, miR-29c-3p increased HK-2 cells apoptosis and ERS upon high glucose-challenge. SIRT1 was a direct target gene of miR-29c-3p in HK-2 cells, which participated in the effects of miR-29c-3p on HK-2 cells. Mechanistically, TUG1 suppressed the expression of miR-29c-3p, thus counteracting its function in downregulating the level of SIRT1. TUG1 regulates miR-29c-3p/SIRT1 and subsequent ERS to relieve high glucose induced renal epithelial cells injury, and suggests a potential role for TUG1 as a promising diagnostic marker of diabetic nephropathy.
AuthorsShaoqiang Wang, Pengfei Yi, Na Wang, Min Song, Wenhui Li, Yingying Zheng
JournalPloS one (PLoS One) Vol. 16 Issue 6 Pg. e0252761 ( 2021) ISSN: 1932-6203 [Electronic] United States
PMID34097717 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • MIRN29C microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • TUG1 long noncoding RNA, human
  • SIRT1 protein, human
  • Sirtuin 1
  • Glucose
Topics
  • Apoptosis
  • Cell Line
  • Diabetic Nephropathies (genetics, metabolism)
  • Endoplasmic Reticulum Stress
  • Epithelial Cells (metabolism)
  • Glucose (metabolism, toxicity)
  • Humans
  • Kidney (cytology)
  • MicroRNAs (genetics, metabolism)
  • RNA, Long Noncoding (genetics, metabolism)
  • Sirtuin 1 (genetics, metabolism)

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