Profibrotic Pathways And Surface Markers Are Upregulated In Fibroblasts Of Striae Distensae
Mimi R. Borrelli, MD, MS1, Michael Januszyk, MD, PhD1, Abra R. Shen, SB1, Shamik R. Mascharak, BS1, Jan Sokol, N/A2, Michael S. Hu, MD2, Rahim Nazerali, MD1, Gordon Lee, MD1, Derrick Wan, MD1, Michael Longaker, MD2, Hermann Lorenz, MD3.
1Stanford, menlo park, CA, USA, 2Stanford, Palo alto, CA, USA, 3Stanford, palo alto, CA, USA.
PURPOSE: Striae distensae are common disfiguring cutaneous lesions but their etiology remains elusive. Dermal fibroblasts likely play an important role in the pathophysiology. We sought to elucidate the key cellular and molecular features distinguishing fibroblasts in striae distensae and normal skin.
METHODS: Striae distensae and normal skin sections were isolated from surgical specimens. Tensile strength and histological structure was compared. Fibroblasts were isolated by flow cytometry for analysis of gene expression using mRNA microarrays. Immunofluorescence staining and flow cytometry were used for confirmation of gene expression data at the protein level.
RESULTS: Striae distensae exhibited reduced tensile strength, more disordered collagen fibers, and decreased epidermal thickness compared to normal skin. There were 296 up-regulated genes in fibroblasts from striae compared to normal skin, including the pro-fibrotic surface marker CD26, and these genes were involved in profibrotic TGFβ and FAK-PI3-AKT-signaling pathways. In contrast, the anti-fibrotic macrophage migration inhibitory factor receptor, CD74, and the AMPK pathway were significantly down-regulated in striae. Increased CD26 and decreased CD74 expression was confirmed by flow cytometry and immunofluorescence staining.CONCLUSION: We elucidate the mechanisms mediating formation of striae distensae and indicate that fibroblasts from striae exhibit increased pro-fibrotic and decreased anti-fibrotic signalings. Up-regulation of CD26 and down-regulation of CD74 highlight these surface markers as promising targets for the development of effective treatment strategies of striae distensae.
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