Mitochondrial CircRNA CircMT‐RNR2 Safeguards Antioxidant Defense to Support Fibroblast Functions in Wound Repair
Source abstract
Abstract
ABSTRACT Diabetic foot ulcers (DFUs) are a debilitating diabetes complication in which mitochondrial dysfunction and oxidative stress are prominent but mechanistically unresolved features. Here, we identify the mitochondria‐encoded circular RNA (mecciRNA) circMT‐RNR2 as a novel modulator of mitochondrial redox homeostasis in human skin wound healing. CircMT‐RNR2 is reduced in DFU patient tissue and diabetic mouse wounds, enriched in dermal fibroblasts, and localized to mitochondria. Its loss impairs fibroblast proliferation, migration, extracellular matrix production, and contraction by destabilizing the mitochondrial antioxidant protein PRDX3, leading to elevated oxidative stress, mitochondrial damage, and mitophagy. In murine and human ex vivo wound models, circMT‐RNR2 knockdown delays healing, whereas overexpression accelerates repair and boosts antioxidant defenses. These findings position circMT‐RNR2 as a mitochondrial guardian of skin healing and a promising therapeutic target for DFU.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Circular RNAs in diseases · Wound Healing and Treatments · Diabetic Foot Ulcer Assessment and Management
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Dermatology and Venereology Division Department of Medicine (Solna) Center For Molecular Medicine Karolinska Institute Stockholm Sweden
Department of Dermatology The Second Hospital of Dalian Medical University College of Integrative Medicine Dalian Medical University Dalian China
Department of Microbiology Tumor and Cell Biology Karolinska Institutet Solna Sweden
Jiangsu Provincial Key Laboratory of Dermatology Hospital for Skin Diseases Institute of Dermatology Chinese Academy of Medical Sciences & Peking Union Medical College Nanjing China
Clinical Microbiology Karolinska University Hospital Solna Sweden
Singapore Centre on Environmental Life Sciences Engineering Nanyang Technological University Singapore Singapore
Department of Plastic and Reconstructive Surgery Karolinska University Hospital Sweden and Department of Molecular Medicine and Surgery Karolinska Institute Stockholm Sweden
Nordiska Kliniken Stockholm Sweden
Department of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden
Funding
Vetenskapsrådet · Karolinska Institutet · Åke Wiberg Stiftelse · LEO Fondet
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