Sustained β-catenin activity in dermal fibroblasts promotes fibrosis by up-regulating expression of extracellular matrix protein-coding genes.

ABSTRACT: Fibrosis is an end-stage response to tissue injury that is associated with loss of organ function as a result of excess extracellular matrix (ECM) production by fibroblasts. In skin, pathological fibrosis is evident during keloid scar formation, systemic sclerosis (SSc) and morphea. Dermal fibroblasts in these fibrotic diseases exhibit increased Wnt/β-catenin signalling, a pathway that is sufficient to cause fibrosis in mice. However, in the context of this complex pathology, the precise pro-fibrotic consequences of Wnt/β-catenin signalling are not known. We found that expression of stabilized β-catenin in mouse dermal fibroblasts resulted in spontaneous, progressive skin fibrosis with thickened collagen fibres and altered collagen fibril morphology. The fibrotic phenotype was predominated

SUBMITTER: Hamburg-Shields E 

PROVIDER: S-EPMC4357547 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature