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

Boudreau, Colton; LeVatte, Terry L.; Jones, Courtney; Gareau, Alison J.; Legere, Stephanie; Bezuhly, Michael

doi:10.1016/j.jss.2020.06.051

Cited by 10 publications

(8 citation statements)

References 42 publications

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“…The effect of angiotensin on type 2 receptors (AT2) is opposed to the one on AT1, since it inhibits fibrosis. Accordingly, Compound 21 (C21), which is an AT2 agonist, has decreased intraperitoneal TGFβ levels in animal subjects and has successfully prevented abdominal adhesion formation [ 15 ].…”

Section: Resultsmentioning

confidence: 99%

Postsurgical Adhesions: Is There Any Prophylactic Strategy Really Working?

Flutur,

Păduraru,

Bolocan

et al. 2023

JCM

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Postoperative adhesions are a frequent complication encountered after surgical procedures, mainly after intraperitoneal interventions. To this day, the pathophysiological mechanism behind the process of adhesions formation is not completely known. There are many strategies proposed as prophylaxis methods, involving surgical techniques, drugs or materials that prevent adhesions and even state of the art technologies such as nanoparticles or gene therapy. The aim of our review is to present these innovative approaches and techniques for postoperative adhesions prevention. After a thorough scientific database query, we selected 84 articles published in the past 15 years that were relevant to our topic. Despite all the recent groundbreaking discoveries, we are at an early stage of understanding the complexity of the adhesion formation mechanism. Further investigations should be made in order to create an ideal product for safe clinical use for prevention.

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Section: Resultsmentioning

confidence: 99%

Postsurgical Adhesions: Is There Any Prophylactic Strategy Really Working?

Flutur,

Păduraru,

Bolocan

et al. 2023

JCM

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“…C21 has been shown to reduce fibrosis associated with myocardial infarction, stroke, renal disease, and idiopathic pulmonary fibrosis [128][129][130][131]. C21 is also reported to reduce intra-peritoneal adhesion formation in mice, and has inhibitory effects on mesothelial cell and peritoneal fibroblast migration, TGF-β levels, and pSMAD2/3 expression, all of which have been shown to contribute to adhesion formation [132].…”

Section: Agents Targeting Angiotensinmentioning

confidence: 97%

Prevention of Post-Operative Adhesions: A Comprehensive Review of Present and Emerging Strategies

et al. 2021

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Post-operative adhesions affect patients undergoing all types of surgeries. They are associated with serious complications, including higher risk of morbidity and mortality. Given increased hospitalization, longer operative times, and longer length of hospital stay, post-surgical adhesions also pose a great financial burden. Although our knowledge of some of the underlying mechanisms driving adhesion formation has significantly improved over the past two decades, literature has yet to fully explain the pathogenesis and etiology of post-surgical adhesions. As a result, finding an ideal preventative strategy and leveraging appropriate tissue engineering strategies has proven to be difficult. Different products have been developed and enjoyed various levels of success along the translational tissue engineering research spectrum, but their clinical translation has been limited. Herein, we comprehensively review the agents and products that have been developed to mitigate post-operative adhesion formation. We also assess emerging strategies that aid in facilitating precision and personalized medicine to improve outcomes for patients and our healthcare system.

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“…In a mouse xenograft model of Dupuytren disease, we have shown that C21 reduces myofibroblast expression and TGF-β transcription [ 18 ]. Additionally, C21 reduces intra-abdominal adhesions in a mouse model [ 23 ]. Given these antifibrotic effects of AT2R engagement, we sought to investigate the role of AT2R signaling in a mouse model of cutaneous wound healing.…”

Section: Introductionmentioning

confidence: 99%

AT2R Activation Improves Wound Healing in a Preclinical Mouse Model

Harrison,

Leong,

Osborne

et al. 2024

Biomedicines

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Abnormal skin healing resulting in chronic wounds or hypertrophic scarring remains a major healthcare burden. Here, the antifibrotic angiotensin II type 2 receptor (AT2R) signaling pathway was modulated to determine its impact on cutaneous wound healing. Balb/c mice received two splinted full-thickness wounds. Topical treatments with the selective AT2R agonist compound 21 (C21) and/or selective antagonist PD123319 or saline vehicle were administered until sacrifice on post-wounding days 7 or 10. The rate of wound re-epithelialization was accelerated by PD123319 and combination treatments. In vitro, C21 significantly reduced human fibroblast migration. C21 increased both collagen and vascular densities at days 7 and 10 post-wounding and collagen I:III ratio at day 10, while PD123319 and combination treatments decreased them. Genes associated with regeneration and repair were upregulated by C21, while PD123319 treatment increased the expression of genes associated with inflammation and immune cell chemotaxis. C21 treatment reduced wound total leukocyte and neutrophil staining densities, while PD123319 increased these and macrophage densities. Overall, AT2R activation with C21 yields wounds that mature more quickly with structural, cellular, and gene expression profiles more closely approximating unwounded skin. These findings support AT2R signal modulation as a potential therapeutic target to improve skin quality during wound healing.

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

Cited by 10 publications

References 42 publications

Postsurgical Adhesions: Is There Any Prophylactic Strategy Really Working?

Postsurgical Adhesions: Is There Any Prophylactic Strategy Really Working?

Prevention of Post-Operative Adhesions: A Comprehensive Review of Present and Emerging Strategies

AT2R Activation Improves Wound Healing in a Preclinical Mouse Model

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