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.