Ogerin Inhibits Development of Post-Operative Abdominal Adhesions in a Murine Model.

BACKGROUND

Adhesions form as a response to peritoneal tissue trauma. Myofibroblast collagen production is key to adhesion formation and ogerin can prevent myofibroblast differentiation in tissue-resident fibroblast populations. In this two-part study, we sought to evaluate ogerin's potential to prevent myofibroblast differentiation, in vitro, and adhesion formation in vivo.

METHODS

We performed a two-part study. (1) In vitro: Human peritoneal fibroblasts were cultured from four pediatric surgical patients. We tested myofibroblast differentiation using alpha smooth muscle actin (α-SMA) and collagen (Col1A1) expression in response to transforming growth factor beta (TGF-β), ogerin, and TGF-β+ogerin versus control. (2) In vivo: Randomized, blinded trial of intraperitoneal ogerin versus control using a murine model. Adhesions were quantified using clinical adhesion scores, histologic measurements, and α-SMA/FAP expression.

RESULTS

In vitro: TGF-β induced differentiation of human peritoneal fibroblasts into pro-fibrotic myofibroblasts increased α-SMA (TGF-β: 2.7 ± 1.2 vs. control: 1.0 ± 0.27, p < 0.01) and Col1A1 expression (TGF-β: 1.2 ± 0.18 vs. control: 1.0 ± 0.12, p = 0.03); a response that was blunted with ogerin treatment (α-SMA: ogerin + TGF-β: 1.2 ± 0.58 vs. TGF-β: 2.7 ± 1.2, p < 0.01; Col1A1: TGF-β+ogerin: 0.79 ± 0.21 vs. TGF-β: 1.2 ± 0.18, p < 0.01). In vivo: Ogerin-treated mice had lower adhesion scores (ogerin: 1.85 ± 1.01; control: 2.95 ± 0.95; p = 0.03) and decreased histologic adhesion area (ogerin: 1.16 ± 1.82 mm2; control: 3.31 ± 3.20 mm2; p = 0.04) compared to controls.

CONCLUSION

Ogerin inhibits TGF-β-induced myofibroblast differentiation in vitro and, blunts adhesion formation in an in vivo murine model. While the complete mechanism of action is not fully elucidated, these results suggest that ogerin may be a translational tool for preventing adhesion formation in patients undergoing abdominopelvic surgery.

TYPE OF STUDY: Laboratory Investigation.

LEVEL OF EVIDENCE: N/A.