伤口愈合
肉芽组织
成纤维细胞
细胞生物学
化学
纤维化
内质网
病理
医学
生物
生物化学
免疫学
体外
作者
Ritu Bansal,Mónica S. Torres,Matthew A. Hunt,Nuoqi Wang,Maria Chatzopoulou,Mansi Manchanda,Evan P. Taddeo,Cynthia Shu,Orian S. Shirihai,Etty Bachar-Wikström,Jakob D. Wikström
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2024-04-02
标识
DOI:10.1172/jci.insight.169213
摘要
Central for wound healing is the formation of granulation tissue, which largely consists of collagen and whose importance stretches past wound healing, including being implicated in both fibrosis and skin aging. Cyclophilin D (CyD) is a mitochondrial protein that regulates the permeability transition pore, known for its role in apoptosis and ischemia-reperfusion. To date, the role of CyD in human wound healing and collagen generation ihas been largely unexplored. Here, we show that CyD was upregulated in normal wounds and venous ulcers, likely adaptive as CyD inhibition impaired re-epithelialization, granulation tissue formation, and wound closure in both human and pig models. Overexpression of CyD increased keratinocyte migration and fibroblast proliferation, whilst its inhibition reduced migration. Independent of wound healing, CyD inhibition in fibroblasts reduced collagen secretion and caused endoplasmic reticulum collagen accumulation, while its overexpression increased collagen secretion. This was confirmed in a Ppif knockout mouse model, which showed a reduction in skin collagen. Overall, this study revealed previously unreported roles of CyD in skin, with implications for wound healing and beyond.
科研通智能强力驱动
Strongly Powered by AbleSci AI