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

Yi Xu1, Yifang Lu1, Geling Liu1

  • 1First Department of Endocrinology, Tangshan Gongren Hospital, Tangshan City, Hebei Province, 063000, China.

Sexual Medicine
|October 17, 2025
PubMed
Abstract

Insights

High glucose causes fibrosis in corpora cavernosa, but Angiotensin (1-7) offers protection by inhibiting the TGF-β1/AKT pathway. This finding reveals a potential therapeutic target for erectile dysfunction.

Area of Science:

  • Endocrinology and Metabolism
  • Urology
  • Molecular Biology

Background:

  • Hyperglycemia is a key driver of atherosclerosis and fibrosis in the corpora cavernosa.
  • Transforming growth factor-β1 (TGF-β1) significantly contributes to fibrotic tissue development in corporal tissue.
  • This process can lead to the replacement of normal corpora cavernosa with fibrotic tissue.

Purpose of the Study:

  • To investigate the role of Angiotensin (1-7) (Ang 1-7) in mitigating fibrosis within the corpora cavernosa.
  • To elucidate the regulatory mechanisms, specifically the TGF-β1/AKT signaling pathway, involved in Ang 1-7's protective effects.

Main Methods:

  • Primary rat corpus cavernosum smooth muscle cells (CCSMCs) were exposed to high glucose (HG) conditions, with or without Ang 1-7 treatment.
  • Protein levels of TGF-β1, Collagen I, TGF-β receptor-I (TβRI), and caveolin-1 (Cav-1) were quantified using western blotting.
  • Reactive oxygen species (ROS), peroxynitrite (ONOO⁻) levels, and intracellular calcium content were measured to assess cellular stress and signaling.

Main Results:

  • High glucose exposure significantly increased TGF-β1 and Collagen I levels, induced oxidative stress, altered the AKT signaling pathway, and elevated intracellular calcium in CCSMCs.
  • Angiotensin (1-7) treatment markedly reduced these HG-induced detrimental effects.
  • The protective action of Ang 1-7 was linked to the downregulation of TGF-β1 and attenuation of oxidative stress.

Conclusions:

  • Angiotensin (1-7) demonstrates a protective effect on CCSMCs against high glucose-induced damage.
  • These beneficial effects are mediated through the modulation of the TGF-β1/AKT signaling pathway.
  • Targeting the TGF-β1/AKT pathway presents a promising therapeutic strategy for managing hyperglycemia-related erectile dysfunction.

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