Acetoacetate ameliorates skin fibrosis by modulating TGF-β1-Smad2/3 signaling pathway.

ABSTRACT: Skin fibrosis is a progressive pathologic outcome of prolonged healing of cutaneous wounds, which has been well accepted as a metabolic disease in a recent study. However, the impact of ketone body metabolism on the development of cutaneous fibrosis remains largely unknown. Here, we found that ketone body metabolism was impaired in both human scars and bleomycin (BLM)-induced skin fibrogenesis of mice by bioinformatics analysis, which was further evidenced by downregulated expression of key modulators of ketone metabolism, including BDH1 (3-hydroxybutyrate dehydrogenase 1), OXCT1 (3-oxoacid CoA-transferase 1), and ACAT1 (acetyl-CoA acetyltransferase 1). With knockdown of OXCT1, a spontaneous onset of fibrosis in normal skin and exacerbation of BLM-induced skin fibrogenesis were observed. I

SUBMITTER: Shang T 

PROVIDER: S-EPMC12666854 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature