Abstract

INTRODUCTION: Striae distensae (SD) are common disfiguring cutaneous lesions but lack effective treatments due to an incomplete understanding of their pathophysiology. Dermal fibroblasts likely play an important role. We investigate the cellular-molecular features distinguishing fibroblasts from human SD and normal skin (NS). We also develop a mouse model of SD.METHODS: Human SD and NS samples were compared for tensile strength and histological structure. Fibroblasts from SD and NS were isolated by fluorescence-activated cell sorting (FACS) for gene expression analysis. Immunofluorescence staining and FACS were used to confirm gene expression data at the protein level. A mouse model of SD formation was created by administering corticosteroids and mechanically loading the dorsal skin.RESULTS: Human SD exhibited reduced tensile strength, more disordered collagen fibers, and epidermal atrophy compared to human NS. There were 296 upregulated genes in SD fibroblasts, including the profibrotic lineage and surface marker CD26. Upregulated genes were involved in profibrotic and mechanoresponsive signaling pathways (TGFbeta and FAK-PI3-AKT-signaling). In contrast, 571 genes were downregulated, including CD74 and genes of the AMPK pathway. Increased CD26 and decreased CD74 expression was confirmed by FACS and immunofluorescence. Similar cutaneous histological and gene expression changes were induced in hypercortisolemic mice by mechanically loading the dorsal skin.CONCLUSIONS: Fibroblasts from human SD exhibit increased profibrotic and decreased antifibrotic signaling. CD26 and CD74 are promising surface markers that may be targeted therapeutically. Our mouse model of SD can be used as a platform to test the efficacy of potential therapeutic agents.

View details for DOI 10.1097/PRS.0000000000009363

View details for PubMedID 35666152