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Angiotensin (1-7) decreases the fibrotic process by modulating the TGF-β1/AKT pathway in rat corpus cavernosum smooth muscle cells

Year: 2025

Type: article

Abstract: Background Hyperglycemia induces the development of cavernosa atherosclerosis and fibrosis, and transforming growth factor-β1 (TGF-β1) plays an important role in the induction, promoting fibrosis in corporal tissue, which replaces the normal corpora cavernosa with fibrotic tissue. Aim This study explored the role of Angiotensin (1-7) (Ang 1-7) and the regulatory mechanism underlying fibrosis in the corpora cavernosa. Methods Primary rat corpus cavernosum smooth muscle cells (CCSMCs) were cultured under normal and high glucose (HG) with or without Ang 1-7. The protein levels of TGF-β1, Collagen I, TGF-β receptor-I (TβRI), and caveolin-1 (Cav-1) were evaluated by western blotting. Reactive oxygen species (ROS) and peroxynitrite (ONOO-) levels in cell culture supernatants were measured by enzyme-linked immunosorbent assay. Intracellular calcium content was determined by flow cytometry. Outcomes High glucose significantly increased the protein levels of TGF-β1 and Collagen I, triggered oxidative stress, modulated the AKT signaling pathway, and elevated intracellular calcium ion levels in CCSMCs. Angiotensin (1-7) treatment significantly attenuated HG-induced adverse effects in CCSMCs. Results The protective effects of Ang 1-7 against fibrosis in HG-exposed CCSMCs were associated with the downregulation of TGF-β1 levels, accompanied by the attenuation of oxidative stress. The Ang1-7-induced effects in CCSMC cells are mediated through the inhibition of the TGF-β1/AKT signaling pathway. Clinical Translation Our studies provide new insights into the critical role of the TGF-β1/AKT signaling pathway in CCSMCs, identifying it as a potential therapeutic target for treating patients with erectile dysfunction. Strengths and Limitations Angiotensin (1-7) is a unique peptide of the renin–angiotensin system with substantial therapeutic potential. This study assessed the therapeutic effect of Ang 1-7 on the fibrotic process and provided new insights for clinical applications. The clinical formulation, drug stability, and in vivo bioactivity of Ang-1-7 remain to be fully investigated. Conclusion Angiotensin (1-7) exerts a protective effect on CCSMCs under HG conditions by modulating the TGF-β1/AKT signaling pathway.

Source: Sexual Medicine

DOI: 10.1093/sexmed/qfaf080