MiR-34a/Sirt1/p53 signaling pathway contributes to cadmium-induced nephrotoxicity: A preclinical study in mice. (1st August 2021)

• Record Type: Journal Article
• Authors: Hao, Rili; Song, Xinyu; Sun-Waterhouse, Dongxiao; Tan, Xintong; Li, Feng; Li, Dapeng
• Is Part Of: Environmental pollution. Volume 282(2021)
• Publication Date: 2021-08-01
• Subjects: Cadmium -- Nephrotoxicity -- miR-34a -- Sirt1 -- p53; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2021.117029
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: Cadmium (Cd), as an environmental pollutant, can lead to nephrotoxicity. However, its nephrotoxicological mechanisms have not been fully elucidated. In this study, Cd (1.5 mg/kg body weight, gavaged for 4 weeks) was found to induce the renal damage in mice, based on indicators including Cd concentration, kidney index, serum creatinine and blood urea nitrogen levels, pro-inflammatory cytokines and their mRNA expressions, levels of Bcl-2, Bax and caspase9, and histopathological changes of the kidneys. Furthermore, Cd-caused detrimental changes through inducing inflammation and apoptosis via the miR-34a/Sirt1/p53 axis. This is the first report on the role of miR-34a/Sirt1/p53 axis in regulating Cd-caused apoptosis and nephrotoxicity in mice. The findings obtained in this study provide new insights into miRNA-based regulation of heavy metal induced-nephrotoxicity. Graphical abstract: Image 1 Highlights: Cadmium induced nephrotoxicity in Kunming mice. Sirt1 suppression was involved in cadmium-induced nephrotoxicity. Cadmium exposure increased the levels of acetylation and phosphorylation p53 and miR-34a. MiR-34a targeted Sirt1 to regulate the cadmium-induced kidney damage.