Overexpression of TNF- α- converting enzyme in fibroblasts augments dermal fibrosis after inflammation

摘要: TNF-α-converting enzyme (TACE) can cleave transmembrane proteins, such as TNF-α, TNF receptors, and epidermal growth factor receptor (EGFR) ligands, to release the extracellular domains from cell surface. Recent studies have suggested that overexpression of TACE may be associated with pathogenesis inflammation fibrosis. To determine roles in fibrosis, transgenic (TACE-Tg) mice, which overexpressed systemically, were generated. As transgene-derived was expressed an inactive form, no spontaneous phenotype developed TACE-Tg mice. However, could converted active form by furin vitro phorbol myristate acetate (PMA) vivo. Subcutaneous injection PMA into mice induced inflammatory infiltration 1 day later subsequent dermal fibrosis 7 days later. Interestingly, degree at significantly higher than wild-type Correspondingly, increased expression type I collagen primary culture fibroblasts derived Furthermore, phosphorylated EGFR treatment. The collective findings suggest activation shed off putative ligands. Subsequently, soluble ligands bind activate on fibroblasts, then increase resulting induction These results also novel therapeutic targets is after diverse disorders skin.