ArticleClinical and translational medicine2022
TGF-β1 mediates pathologic changes of secondary lymphedema by promoting fibrosis and inflammation.
Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Effectiveness of physical therapy for lower limb lymphedema in gynecological cancer survivors: a systematic review of randomized controlled trials.Frontiers in oncology · 2026Pooled it
- Lymphatic dysfunction and ZFP36 deficiency contribute to myxomatous valve degeneration in Marfan syndrome mice.The Journal of clinical investigation · 2026Article
- 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
- Tamoxifen attenuates postsurgical hindlimb swelling and soft-tissue fibrosis in a rat model of secondary lymphatic injury.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Critical role of keratinocytes and protease-activated receptor 2 in secondary lymphedema development.Clinical and translational medicine · 2026Article
- Identification of a Cytokine Biomarker for Prognostic Modeling of Breast Cancer-Related Lymphedema.Cancer research communications · 2026Article
- Poria cocos-derived exosome-like nanoparticles ameliorate lymphedema by reprogramming fibroblast metabolism via enhanced TCA cycle flux.Journal of nanobiotechnology · 2026Article
- Exosomes derived from ADSCs suppress the fibrosis process of derma in secondary lymphedema.Scientific reports · 2026Article
- Molecular mechanisms of ovarian fibrosis.Molecular human reproduction · 2026Review
- Comprehensive overview of management and risk assessment of breast cancer-related lymphedema: a multidisciplinary approach.Frontiers in oncology · 2026Review
- Breast Cancer-Related Lymphedema: Nursing-Led Strategies - A Narrative Review.Journal of multidisciplinary healthcare · 2026Review
- Mechanisms and treatments of lymphedema.Frontiers in immunology · 2026Review
- Therapeutic targeting of local metabolic dysfunction in secondary lymphedema: mechanisms and opportunities.Frontiers in physiology · 2026Review
- AI-Empowered Mechanomedicine for Cancer-Related Lymphedema.Research (Washington, D.C.) · 2026Review
- Layer-Specific Assessment of Dermal Thickness and Stiffness Using Shear Wave Elastography in Gynecologic Cancer-Related Lower-Limb Lymphedema: An Exploratory Cross-Sectional Study.International journal of general medicine · 2026Article
- A lymphadenectomy and irradiation-induced rat lymphedema model exhibits persistent dermal backflow and region-dependent fibrosis-associated remodeling.Frontiers in cell and developmental biology · 2026Article
- Do not mistake symptomatic improvement for disease modification: therapeutic endpoints in secondary lower-extremity lymphedema require inflammation-fibrosis anchoring.Frontiers in immunology · 2026Review
- Epigenetic reprogramming via EZH2 inhibition rescues fibroadipose pathogenesis in secondary lymphedema through activating PPARγ signaling.Journal of orthopaedic translation · 2025Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
backgroundSecondary lymphedema is a common complication of cancer treatment, and previous studies have shown that the expression of transforming growth factor-beta 1 (TGF-β1), a pro-fibrotic and anti-lymphangiogenic growth factor, is increased in this disease. Inhibition of TGF-β1 decreases the severity of the disease in mouse models; however, the mechanisms that regulate this improvement remain unknown.
methodsExpression of TGF-β1 and extracellular matrix molecules (ECM) was assessed in biopsy specimens from patients with unilateral breast cancer-related lymphedema (BCRL). The effects of TGF-β1 inhibition using neutralizing antibodies or a topical formulation of pirfenidone (PFD) were analyzed in mouse models of lymphedema. We also assessed the direct effects of TGF-β1 on lymphatic endothelial cells (LECs) using transgenic mice that expressed a dominant-negative TGF-β receptor selectively on LECs (LEC
resultsThe expression of TGF-β1 and ECM molecules is significantly increased in BCRL skin biopsies. Inhibition of TGF-β1 in mouse models of lymphedema using neutralizing antibodies or with topical PFD decreased ECM deposition, increased the formation of collateral lymphatics, and inhibited infiltration of T cells. In vitro studies showed that TGF-β1 in lymphedematous tissues increases fibroblast, lymphatic endothelial cell (LEC), and lymphatic smooth muscle cell stiffness. Knockdown of TGF-β1 responsiveness in LEC
conclusionsOur results show that TGF-β1 is an essential regulator of ECM deposition in secondary lymphedema and that inhibition of this response is a promising means of treating lymphedema.
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