Work

Hyperlipidemia-induced metabolic dysregulation impairs tendon homeostasis: the role of TGF-β/Smad2 signaling pathway in lipid-mediated extracellular matrix remodeling

Year: 2026

Type: article

Abstract: Background Hyperlipidemia is a globally prevalent metabolic disorder, and the lipid metabolic dysregulation it induces is closely associated with the onset and progression of tendon pathologies, which are typically characterized by ECM dyshomeostasis, disorganized collagen fiber structure and impaired biomechanical properties in the affected tendons. The TGF- β signaling pathway serves as a central regulator of tendon ECM metabolic homeostasis, among which the TGF-β/Smad2 axis can directly mediate the balanced regulation of collagen synthesis and degradation in tendons, yet its specific role and underlying molecular mechanism in hyperlipidemia-induced tendon ECM dysfunction remain poorly defined. Methods We examined how oxidized lipids affect the TGF- β /Smad2 signaling axis in tendon tissue. Specifically, we assessed TβRII localization within lipid rafts, TGF-β activation, downstream transcription of Col1a1 and lysyl oxidase (LOX), and matrix metalloproteinase-1 (MMP-1) activity. Results Oxidized lipids disrupted T β RII localization in lipid rafts, leading to impaired TGF-β activation. This suppressed Smad2 signaling, decreased Col1a1 transcription and LOX expression, and increased MMP-1 activity. Consequently, tendon collagen synthesis declined while degradation rose, undermining structural integrity and intrinsic repair capacity. Conclusion Hyperlipidemia-driven suppression of the TGF- β /Smad2 axis is the critical mechanism linking metabolic dysregulation to tendon matrix failure. Restoring TGF-β/Smad2 signaling represents a promising therapeutic strategy to mitigate hyperlipidemia-induced tendon damage and poor healing.

Source: Frontiers in Medicine

DOI: 10.3389/fmed.2026.1820393

Authors: Peiyang Shang, Renxuan Li, Yan Xia, Zhen Wang, Renhao Yang, Qingge Fu

Institutions: Shanghai University of Traditional Chinese Medicine, Shanghai Jiao Tong University, Ruijin Hospital

Language: English

Topic: Tendon Structure and Treatment

Subfield: Orthopedics and Sports Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801