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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.
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.
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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