The Selective Angiotensin II Type 2 Receptor Agonist Compound 21 Reduces Abdominal Adhesions in Mice

Colton Boudreau, Terry LeVatte, Courtney Jones, Alison Gareau, Stephanie Legere, Michael Bezuhly

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

10 Citas (Scopus)

Resumen

Background: Abdominal adhesions (AAs) are post-traumatic fibrous bands that connect visceral and/or peritoneal surfaces, leading to possible long-term complications. The effect of a novel antifibrotic selective angiotensin II type 2 receptor agonist, compound 21 (C21) on AA formation was assessed in a murine model. Methods: Female BALB/c mice were laparotomized and the cecum and overlying parietal peritoneum abraded. C21 (10 μg/kg) or saline (vehicle) were administered orally or intraperitoneally daily. Mice were sacrificed 8 days after surgery, adhesions graded, and peritoneal fluid collected for transforming growth factor (TGF)-β levels. Laparotomy incisions were excised for immunohistochemistry. In vitro, scratch assays were performed using primary parietal peritoneal fibroblasts and visceral mesothelial cells treated with C21 (10 μM), angiotensin II (1 μM), or both. Western blot analysis of primary cell lysates was performed for total and phosphorylated SMAD 2/3. Results: Oral and intraperitoneal C21 reduced AA formation and TGF-β levels in peritoneal fluid. Surgical incisions demonstrated decreased α-smooth muscle actin expression in C21-treated animals, but no difference in vascularity, macrophage infiltration, collagen I/III distribution and density, and dermal thickness. Migration and expression of phosphorylated SMAD 2/3 was reduced in parietal peritoneal fibroblasts and visceral mesothelial cells treated with C21. Conclusions: Local and systemic C21 administration reduced or completely prevented AA formation. These findings may be attributed to decreased intraperitoneal TGF-β in vivo and decreased migration of peritoneal fibroblasts and visceral mesothelial cells. Importantly, C21 did not have histologically quantifiable effects on laparotomy wounds, suggesting C21 could reduce AA formation without compromising laparotomy healing.

Idioma originalEnglish
Páginas (desde-hasta)231-242
Número de páginas12
PublicaciónJournal of Surgical Research
Volumen256
DOI
EstadoPublished - dic. 2020

Nota bibliográfica

Funding Information:
Funding: This work was supported by an Izaak Walton Killam Health Center research, Canada grant.

Publisher Copyright:
© 2020 Elsevier Inc.

ASJC Scopus Subject Areas

  • Surgery

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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