한빛사논문
- 조회317
Sally Min 1*, Ki-Myo Kim 1*, Jun Ho Park 1, Mihyun Lee 1, Joseph Hwang 1, Ji-Ung Park 1
1Department of Plastic and Reconstructive Surgery, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea.
*Sally Min and Ki-Myo Kim contributed equally to this work.
Corresponding author: Ji-Ung Park, M.D., Ph.D.
Abstract
Background: Keloid is a dermal fibrotic disorder characterised by excessive extracellular matrix production by fibroblasts. Despite the significance of mechanostimulation in fibrotic diseases, its association with keloid pathophysiology or treatment remains unexplored.
Objective: We investigated the role of mechanical force in keloid formation and elucidated the significance of Rho-associated coiled-coil-containing kinase 1 (ROCK1) as a mechanoresponsive target for keloid treatment.
Methods: Patient-derived keloid fibroblasts (KFs) were subjected to cyclic stretching ranging from 0 to 20% elongation using a cell-stretching system. We observed the inhibitory effects of the ROCK1 inhibitor Y27632 on KFs and keloid formation. Validation was performed using keloid xenograft severe combined immune-deficient (SCID) mouse model.
Results: ROCK1 was overexpressed in KFs isolated from patients. Cyclic stretching induced fibroblast proliferation and actin polymerisation by activating Rho/ROCK1 signalling. Treatment with Y27632 downregulated fibrotic markers, reduced the migration capacity of KFs, and induced extensive actin cytoskeleton remodelling. In keloid xenograft SCID mouse model, Y27632 effectively suppressed keloid formation, mitigating inflammation and fibrosis.
Conclusions: The ROCK1 inhibitor Y27632 is a promising molecule for keloid treatment, exerting its effects through actin cytoskeleton remodelling and nuclear inhibition of fibrotic markers in keloid pathogenesis.
논문정보
- Research article
- 2024년 10월 (BRIC 등록일 2024-10-14)
- 국내 연구진
- 바이오·의료융합 > 바이오소재
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