A potential role of the renin-angiotensin-aldosterone system in epithelial-to-mesenchymal transition-induced renal abnormalities: Mechanisms and therapeutic implications. (August 2019)

• Record Type: Journal Article
• Authors: Balakumar, Pitchai; Sambathkumar, Ramanathan; Mahadevan, Nanjaian; Muhsinah, Abdullatif Bin; Alsayari, Abdulrhman; Venkateswaramurthy, Nallasamy; Jagadeesh, Gowraganahalli
• Is Part Of: Pharmacological research. Volume 146(2019)
• Publication Date: 2019-08
• Subjects: ACE angiotensin-converting enzyme -- α-SMA alpha-smooth muscle actin -- Ang (1–7) angiotensin (1-7) -- Ang II angiotensin II -- AT1 receptor angiotensin II-type 1 receptor -- ECM extracellular matrix -- EGFR epidermal growth factor receptor -- EMT epithelial-to-mesenchymal transition -- ERK extracellular signal-regulated kinase -- FSP-1 fibroblast-specific protein-1 -- MAF 25-O-methylalisol F -- miRs MicroRNAs -- NRK52E normal rat tubular epithelial cell lines -- PPARγ peroxisome proliferator-activated receptor gamma -- PZA poricoic acid ZA -- RAAS renin-angiotensin-aldosterone system -- SHRs spontaneously hypertensive rats -- TGF-β transforming growth factor-beta; Angiotensin II -- Angiotensin (1-7) -- Aldosterone -- Renal epithelial-to-mesenchymal transition -- Renal fibrosis -- RAAS interventions; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2019.104314
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: Epithelial-to-mesenchymal transition (EMT) is an orchestrated event where epithelial cells progressively undergo biochemical changes and transition into mesenchymal-like cells by gradually losing their epithelial characteristics. EMT plays a crucial pathologic role in renal abnormalities, especially renal fibrosis. A number of bench studies suggest the potential involvement of renin-angiotensin-aldosterone system (RAAS) in renal EMT process and associated renal abnormalities. EMT appears to be an important pathologic mechanism for the deleterious renal effects of angiotensin II and aldosterone, the two major RAAS components. Mechanistically, the renal RAAS-TGF-β-Smad3 signalling pathway plays an important pathologic role in EMT-associated renal abnormalities. Intriguingly, the RAAS antagonists such as losartan, telmisartan, eplerenone, and spironolactone have the potential to prevent renal EMT in bench studies. This review describes the key mechanistic role of RAAS overactivation in EMT-induced renal abnormalities. Moreover, drugs interrupting the RAAS at different levels in the cascade ameliorating the EMT-associated renal abnormalities are described.