NRF2 Shortage in Human Skin Fibroblasts Dysregulates Matrisome Gene Expression and Affects Collagen Fibrillogenesis

NRF2 is a master regulator of the antioxidative response that was recently proposed as potential extracellular matrix (ECM) gene expression. Fibroblasts are major ECM producers in all connective tissues, including dermis. A better understanding NRF2-mediated regulation skin fibroblasts thus great interest for homeostasis maintenance and aging protection. In this study, we investigate impact downregulation on matrisome expression deposits human primary dermal fibroblasts. RNA-sequencing?based transcriptome analysis silenced shows genes most regulated sets, highlighting relevance program these cells. Using complementary light electron microscopy methods, show deprivation results reduced collagen I biosynthesis impacts fibril deposition. Moreover, identify ZNF469, putative transcriptional biosynthesis, target NRF2. Both ZNF469 derived from Brittle Corneal Syndrome patients carrying variants ZNF469 Our study orchestrates through direct or indirect mechanisms could be prioritized to health disease.