Zhang, J.; Brown, R.; Hogan, M.V.; Wang, J.H.-C. Mitigating Scar Tissue Formation in Tendon Injuries: Targeting HMGB1, AMPK Activation, and Myofibroblast Migration All at Once. Pharmaceuticals2023, 16, 1739.
Zhang, J.; Brown, R.; Hogan, M.V.; Wang, J.H.-C. Mitigating Scar Tissue Formation in Tendon Injuries: Targeting HMGB1, AMPK Activation, and Myofibroblast Migration All at Once. Pharmaceuticals 2023, 16, 1739.
Zhang, J.; Brown, R.; Hogan, M.V.; Wang, J.H.-C. Mitigating Scar Tissue Formation in Tendon Injuries: Targeting HMGB1, AMPK Activation, and Myofibroblast Migration All at Once. Pharmaceuticals2023, 16, 1739.
Zhang, J.; Brown, R.; Hogan, M.V.; Wang, J.H.-C. Mitigating Scar Tissue Formation in Tendon Injuries: Targeting HMGB1, AMPK Activation, and Myofibroblast Migration All at Once. Pharmaceuticals 2023, 16, 1739.
Abstract
Tendon injuries, while prevalent, present a significant challenge in fully restoring their structural and functional integrity. Utilizing alpha-smooth muscle actin (α-SMA)-Ai9-scleraxis (Scx)-green fluorescent protein (GFP) transgenic mice, which exhibit both Scx (a tendon cell marker) and α-SMA (a myofibroblast marker), we explored Met's effects on tendon healing and repair and its mechanisms of action. Our findings revealed that intraperitoneal (IP) injections of Met -administered before or after injury, as well as both - effectively prevent the release of HMGB1 into the tendon matrix and reduce circulating levels of HMGB1. Additionally, Met treatment increased and activated AMPK and suppressed TGF-β1 levels within the healing tendon. These interventions also improved tendon healing by blocking the migration of α-SMA+ myofibroblasts, reducing the prevalence of disorganized collagen fibers and collagen type III, and enhancing the presence of collagen type I. These outcomes highlight Met's anti-fibrotic properties on acutely injured tendons and suggest its potential for repurposing as a therapeutic agent to minimize scar tissue formation in tendon injuries, which could have profound implications in clinical practice.
Keywords
Metformin; tendon injury; scar tissue
Subject
Medicine and Pharmacology, Orthopedics and Sports Medicine
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
