Type V Collagen as a Critical Regulator of Fibrillar Matrix Remodeling in a Murine Model of Systemic Sclerosis.

Abstract

Type V collagen (Col V) has been implicated in the development of fibrosis in systemic sclerosis (SSc). In this study, we aimed to investigate the role of Col V in fibrillar matrix remodeling and fibroblast differentiation using an experimental SSc model. Skin fibroblasts from healthy C57BL/6 mice were stimulated in vitro with 25 and 50 μg of Col V to assess fibrillar collagen expression. An SSc model was induced in C57BL/6 mice by immunization with Col V emulsified in Freund's adjuvant (IMU-COLV), with animals assigned to 15-, 30-, and 45-day IMU-COLV or control groups. In vitro, Col V stimulation caused a dose-dependent increase in myofibroblast markers (α-SMA, Col I, and Col V) and altered fibrillar collagen structure. Immunofluorescence revealed thickened Col V and Col III fibrils around myofibroblasts and the formation of a spiderweb-like matrix. In vivo, fibrosis progressed over time, characterized by increased myofibroblast accumulation and elevated Col I and Col V levels. Histological analysis revealed fibrillar disorganization and aggregated collagen fibers resembling early-stage human SSc. These findings suggest that enhanced Col V synthesis disrupts the fibrillar matrix, promoting myofibroblast differentiation and collagen deposition, which are hallmarks of SSc-related fibrosis.