ArticleJCI insight2023
PPARγ agonist treatment reduces fibroadipose tissue in secondary lymphedema by exhausting fibroadipogenic PDGFRα+ mesenchymal cells.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 2 syntheses or guidelines pooled it, 10 citations in OpenAlex.
- Animal Models of Lymphaticovenous Anastomosis: A Systematic Review of Current Evidence and Future Directions in Translational Research.Microsurgery · 2026Pooled it
- Pharmacotherapy agents in prevention and treatment of breast cancer-related lymphedema: a systematic scoping review.Frontiers in oncology · 2026Pooled it
- Rewiring Cellular Context as A Central Mechanism Governing Cancer Stem Cell Survival: Insights from ESC Comparisons.Stem cell reviews and reports · 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
- PPARγ signalling pathway: molecular mechanisms and therapeutic potential in ligamentum flavum hypertrophy and lumbar spinal stenosis.Journal of translational medicine · 2026Review
- PPAR-γ suppresses macrophage senescence and allergic airway inflammation through controlling lipid metabolic pathways.EBioMedicine · 2026Article
- Renoprotective effect of dulaglutide in L-NAME-induced hypertensive nephropathy in rats: insight into the roles of PPAR-gamma and VEGF.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Article
- From stasis to systematics: deciphering the pathophysiology of secondary lymphedema through omics.Frontiers in immunology · 2026Review
- Therapeutic targeting of local metabolic dysfunction in secondary lymphedema: mechanisms and opportunities.Frontiers in physiology · 2026Review
- Epigenetic reprogramming via EZH2 inhibition rescues fibroadipose pathogenesis in secondary lymphedema through activating PPARγ signaling.Journal of orthopaedic translation · 2025Article
- Advances in etiology, pathophysiology, diagnosis, and management of lymphedema: a comprehensive review.Frontiers in medicine · 2025Review
- PPARγ attenuates cellular senescence of alveolar macrophages in asthma-COPD overlap.Respiratory research · 2024Article
- PPARγ Attenuates Cellular Senescence of Alveolar Macrophages in Asthma- COPD Overlap.Research square · 2024Article
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 2 countries.
Funding
Abstract
Secondary lymphedema occurs in up to 20% of patients after lymphadenectomy performed for the surgical management of tumors involving the breast, prostate, uterus, and skin. Patients develop progressive edema of the affected extremity due to retention of protein-rich lymphatic fluid. Despite compression therapy, patients progress to chronic lymphedema in which noncompressible fibrosis and adipose tissue are deposited within the extremity. The presence of fibrosis led to our hypothesis that rosiglitazone, a PPARγ agonist that inhibits fibrosis, would reduce fibrosis in a mouse model of secondary lymphedema after hind limb lymphadenectomy. In vivo, rosiglitazone reduced fibrosis in the hind limb after lymphadenectomy. Our findings verified that rosiglitazone reestablished the adipogenic features of TGF-β1-treated mesenchymal cells in vitro. Despite this, rosiglitazone led to a reduction in adipose tissue deposition. Single-cell RNA-Seq data obtained from human tissues and flow cytometric and histological evaluation of mouse tissues demonstrated increased presence of PDGFRα+ cells in lymphedema; human tissue analysis verified these cells have the capacity for adipogenic and fibrogenic differentiation. Upon treatment with rosiglitazone, we noted a reduction in the overall quantity of PDGFRα+ cells and LipidTOX+ cells. Our findings provide a framework for treating secondary lymphedema as a condition of fibrosis and adipose tissue deposition, both of which, paradoxically, can be prevented with a pro-adipogenic agent.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.