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.
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