TGF-β-mediated epithelial-mesenchymal transition of keratinocytes promotes fibrosis in secondary lymphedema.

ABSTRACT: Secondary lymphedema is characterized by fibrosis and impaired lymphatic function. Although TGF-β is a key regulator of fibrosis in this disease, the cellular mechanisms regulating this process remain unknown. Epithelial-mesenchymal transition (EMT), a mechanism by which TGF-β induces fibrosis in other skin diseases, is characterized by loss of epithelial cell markers and cellular polarity, upregulation of fibrotic gene expression, and gain of migratory capacity. Using clinical lymphedema biopsy specimens and animal models, we show that keratinocytes in the basal layer of the epidermis undergo EMT in lymphedematous skin, migrate into the dermis, and contribute to dermal fibrosis. In vitro studies using cultured primary human keratinocytes treated with lymphatic fluid from the affected limb

SUBMITTER: Park HJ 

PROVIDER: S-EPMC12487678 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature