Acute kidney injury (AKI) often progresses to chronic kidney disease (CKD), presenting a significant clinical challenge. The renin-angiotensin system (RAS), particularly the protective arm involving Angiotensin-(1-7) (Ang-(1-7)), offers a potential therapeutic target to mitigate this progression. This study explores the effects of Ang-(1-7) in a murine model of ischemia-reperfusion (I/R) injury-induced AKI. Methods. Adult male Balb/c mice were subjected to bilateral renal I/R injury to induce AKI. Mice were then treated with various doses of Ang-(1-7). Key methods included enzyme-linked immunosorbent assay (ELISA) for serum biomarkers, immunohistochemistry for tissue-specific protein expression, and Western blotting for signaling pathway analysis. Key endpoints included serum levels of Angiotensin II (Ang II), Transforming Growth Factor-β1 (TGF-β1), Collagen I, and Superoxide Dismutase (SOD). Results. Ang-(1-7) treatment significantly reduced serum Ang II and TGF-β1 levels and decreased renal Collagen I expression. Notably, a dose-dependent increase in SOD was observed, indicating enhanced antioxidant defense. Additionally, Ang-(1-7) administration led to a marked reduction in renal fibrosis markers and inflammatory cytokines, including TGF-β1 and Collagen I, particularly in the high-dose group. The treatment also modulated the expression of key proteins involved in the RAS pathway, such as increased Angiotensin-Converting Enzyme 2 (ACE2) and decreased Angiotensin II Receptor Type 1 (AT1R) expression. Conclusion. This study highlights the novel therapeutic potential of Ang-(1-7) in preventing AKI progression to CKD by modulating the RAS towards a protective state. The findings provide a strong rationale for further clinical investigation of Ang-(1-7) or Mas receptor agonists as viable therapeutic strategies in kidney disease management.
Qiu et al. (Tue,) studied this question.