A multiomics analysis identifies retinol metabolism in fibroblasts as a key pathway in wound healing
Impaired wound healing poses a major and increasingly frequent health problem. Among the key players in the healing process are fibroblasts, but their metabolic profile in healing wounds is largely unknown. Using a combination of transcriptomics, targeted proteomics, and metabolomics, we identified retinol metabolism as a top regulated pathway in wound fibroblasts. This is functionally relevant, since even a mild retinol deficiency caused a delay in wound closure and reepithelialization, which mainly resulted from misdirected keratinocyte migration on the new granulation tissue. Quantitative proteomics identified integrin subunit α11 as a less abundant protein in wounds of mice subjected to a retinol-deficient diet. Reduced levels of this fibroblast-specific protein likely altered the granulation tissue matrix, which in turn affected reepithelialization. These results provide a comprehensive overview of the transcriptome, proteome, and metabolome of wound fibroblasts and identify retinol metabolism in fibroblasts as a key regulator of tissue repair.
Authors
- Elizabeta Madzharova (ORCID: https://orcid.org/0000-0001-8827-8514)
- Norbert B. Ghyselinck (ORCID: https://orcid.org/0000-0003-4042-6818)
- Mateusz S. Wietecha (ORCID: https://orcid.org/0000-0001-6600-8206)
- Marcus Höring (ORCID: https://orcid.org/0000-0002-3651-392X)
- Till Wüstemann
- Gerhard Liebisch (ORCID: https://orcid.org/0000-0003-4886-0811)
- Ulrich auf dem Keller (ORCID: https://orcid.org/0000-0002-3431-7415)
- Sabine Werner (ORCID: https://orcid.org/0000-0001-7397-8710)
- Nicola Zamboni (ORCID: https://orcid.org/0000-0003-1271-1021)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- ETH Zurich (CH)
- University of Illinois Chicago (US)
- Institut de génétique et de biologie moléculaire et cellulaire (FR)
- University of Regensburg (DE)
- Université de Strasbourg (FR)
- Technical University of Denmark (DK)
Publication Details
- Journal
- JCI Insight
- Published
- 2025-10-16
- DOI
- https://doi.org/10.1172/jci.insight.194188
- Citations
- 1
- Primary Topic
- Wound Healing and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 1.03
Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Eidgenössische Technische Hochschule Zürich
- Universität Zürich
- Universitätsspital Zürich