Nicotinamide N-Methyltransferase drives fibroblast activation and skin fibrosis in systemic sclerosis

ABSTRACT: Systemic sclerosis (SSc) is characterized by progressive skin and organ fibrosis driven by persistently activated fibroblasts, however, the mechanisms of dermal fibroblast (DF) activation remain unclear. Nicotinamide N-methyltransferase (NNMT) has been linked to fibrosis in other diseases, but its relevance to SSc fibrosis has not been tackled. Here, we aimed to assess whether NNMT drives DF activation using RNA-seq in TGFβ-stimulated primary human DFs with siRNA-mediated NNMT knockdown (KD). We futher explored the involvement of transcription factors ATF4, SOX9, and SRF, which drive ECM gene expression and collagen secretion. These results identify a TGFβ–NNMT–ATF4/SOX9/SRF axis that sustains DF activation and fibrosis in SSc, positioning NNMT as a potential therapeutic target to limit fi

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Homo sapiens

SUBMITTER: Anela Tosevska 

PROVIDER: E-MTAB-17206 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress