A multi-omics 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 re-epithelialization, which mainly resulted from misdirected keratinocyte migration on the new granulation tissue. Quantitative proteomics identified integrin alpha 11 (Itga11) 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 re-epithelialization. These results provide a comprehensive overview on the transcriptome, proteome and metabolome of wound fibroblasts and identify retinol metabolism in fibroblasts as a key regulator of tissue repair.