ArticleJCI insight2025
TGF-β-mediated epithelial-mesenchymal transition of keratinocytes promotes fibrosis in secondary lymphedema.
Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Lymphatic Endothelial Cells in Health and Disease.MedComm · 2026Review
- Pan-Peroxisome Proliferator-Activated Receptor Agonist IVA337 Alleviates Secondary Lymphedema via Inhibiting TGFβ/SMAD2/3 Signaling Pathway.bioRxiv : the preprint server for biology · 2026Article
- Keratinocytes: A key player in skin immunity and their emerging roles in secondary lymphedema.JID innovations : skin science from molecules to population health · 2026Review
- Critical role of keratinocytes and protease-activated receptor 2 in secondary lymphedema development.Clinical and translational medicine · 2026Article
- Radiotherapy-Induced Skin Fibrosis: Pathophysiology, Emerging Therapeutics, and the Role of Dermatology.American journal of clinical dermatology · 2026Review
- Poria cocos-derived exosome-like nanoparticles ameliorate lymphedema by reprogramming fibroblast metabolism via enhanced TCA cycle flux.Journal of nanobiotechnology · 2026Article
- Long-term cytokine exposure remodels the methylome and transcriptome of recessive dystrophic epidermolysis bullosa keratinocytes - a bioinformatic analysis.Frontiers in cell and developmental biology · 2026Article
- Therapeutic targeting of local metabolic dysfunction in secondary lymphedema: mechanisms and opportunities.Frontiers in physiology · 2026Review
- From stasis to systematics: deciphering the pathophysiology of secondary lymphedema through omics.Frontiers in immunology · 2026Review
- Do not mistake symptomatic improvement for disease modification: therapeutic endpoints in secondary lower-extremity lymphedema require inflammation-fibrosis anchoring.Frontiers in immunology · 2026Review
- Epithelial-mesenchymal transition in cutaneous fibrosis disease: from mechanisms to therapy.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
10 authors.
Funding
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 limbs of patients with secondary lymphedema resulted in a TGF-β-mediated increased expression of EMT markers. We show for the first time that EMT is activated by TGF-β in secondary lymphedema and that this process plays an important role in regulating skin fibrosis in this disease.
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Registered trials
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