Circ_0000491 Promotes Apoptosis, Inflammation, Oxidative Stress, and Fibrosis in High Glucose-Induced Mesangial Cells by Regulating miR-455-3p/Hmgb1 Axis.

Abstract

BACKGROUND:

Diabetic nephropathy (DN) is a severe microvascular complication of diabetes. Recently, many circular RNAs can exert crucial roles in DN progression. This study intended to explore the role and mechanism of circ_0000491 in DN.

METHODS:

The DN mouse model was constructed by streptozotocin injection, and the DN cell model was established using high glucose (HG) treatment in mouse mesangial cells (SV40-MES13). The expression of circ_0000491 and microRNA-455-3p (miR-455-3p) was detected by quantitative real-time polymerase chain reaction. Cell apoptosis was evaluated by flow cytometry. The expression levels of high-mobility group box 1 (Hmgb1) protein, apoptosis-related proteins, and fibrosis-related proteins were examined by the Western blot assay. The release of inflammatory cytokines was assessed by enzyme-linked immunosorbent assay. The oxidative stress factors were analyzed by corresponding kits. The predicted interaction between miR-455-3p and circ_0000491 or Hmgb1 was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay.

RESULTS:

Circ_0000491 was overexpressed in the DN mouse model and HG-induced SV40-MES13 cells. Knockdown of circ_0000491 weakened HG-induced apoptosis, inflammation, oxidative stress, and fibrosis in SV40-MES13 cells. miR-455-3p was a direct target of circ_0000491, and miR-455-3p inhibition could reverse the role of circ_0000491 silencing in HG-induced SV40-MES13 cells. Moreover, Hmgb1 was a target gene of miR-455-3p, and miR-455-3p played a protective role against HG-induced cell injury by targeting Hmgb1. In addition, circ_0000491 regulated Hmgb1 expression by sponging miR-455-3p.

CONCLUSION:

Circ_0000491 knockdown inhibited HG-induced apoptosis, inflammation, oxidative stress, and fibrosis in SV40-MES13 cells by regulating miR-455-3p/Hmgb1 axis.

• Authors: Jing Wang, Shifeng Yang, Wendong Li, Ming Zhao, Kai Li
• Journal: Nephron (Nephron) Vol. 146 Issue 1 Pg. 72-83 ( 2022) ISSN: 2235-3186 [Electronic] Switzerland
• PMID: 34474408 (Publication Type: Journal Article)
• Copyright: © 2021 S. Karger AG, Basel.

Chemical References

• HMGB1 Protein
• HMGB1 protein, human
• MIRN155 microRNA, human
• MicroRNAs
• RNA, Circular
• Glucose

Topics

• Animals
• Apoptosis (drug effects, genetics)
• Case-Control Studies
• Diabetic Nephropathies (metabolism)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Fibrosis
• Glomerular Mesangium (drug effects, metabolism)
• Glucose (administration & dosage, toxicity)
• HMGB1 Protein (metabolism)
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• MicroRNAs (metabolism)
• Oxidative Stress (drug effects, genetics)
• RNA, Circular (genetics)
• Up-Regulation