Bone Morphogenetic Protein-6 Inhibits Fibrogenesis in Scleroderma Offering Treatment Options for Fibrotic Skin Disease

摘要

BMP6 is known to be crucial for regulating embryonic skin development. This study assessed the role of BMP6 in dermal fibrosis. We detected that BMP6 is significantly increased in skin-derived fibroblasts of patients with localized scleroderma. Moreover, it was shown that BMP6 significantly impacts proliferation, migration, cytoskeletal organization, and collagen expression, as well as activity of the major pro-fibrogenic transcription factor AP-1 in dermal fibroblasts. The importance of BMP6 in dermal fibrosis was further confirmed in an in vivo model of dermal fibrosis in which BMP6-deficient mice showed significantly enhanced fibrosis compared with wild-type mice. Conversely, application of recombinant BMP6 significantly ameliorated dermal fibrosis in this preclinical bleomycin-induced sclerosis model, and herewith provided proof of concept for the successful treatment of this fibrotic skin disease.