ArticleScientific reports2017
Hydrolysis of Hyaluronic Acid in Lymphedematous Tissue Alleviates Fibrogenesis via T
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Hyaluronidase attenuates radiation-induced skin fibrosis through extracellular matrix remodeling and suppression of inflammatory-profibrotic signaling.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- From permeation enhancer to therapeutic enabler: Advances, applications, and translational perspectives in hyaluronidase-based drug delivery.Materials today. Bio · 2026Review
- Agarose Gel Electrophoresis Reveals the Molecular Weight Distribution of Hyaluronan Produced by Orbital Fibroblasts.Gels (Basel, Switzerland) · 2025Article
- Characteristics and advances in signaling pathways, cellular communication, cell junctions, and oxidative stress in lymphedema.Frontiers in cell and developmental biology · 2025Review
- Improved lymphangiogenesis around vascularized lymph node flaps by periodic injection of hyaluronidase in a rodent model.Scientific reports · 2024Article
- The Role of Inflammation in Lymphedema: A Narrative Review of Pathogenesis and Opportunities for Therapeutic Intervention.International journal of molecular sciences · 2024Review
- Molecular pathophysiology of secondary lymphedema.Frontiers in cell and developmental biology · 2024Review
- Analysis of CD4Gland surgery · 2023Article
- Acquired lymphedema: Molecular contributors and future directions for developing intervention strategies.Frontiers in pharmacology · 2022Review
- Analysis of Human Hyaluronan Synthase Gene Transcriptional Regulation and Downstream Hyaluronan Cell Surface Receptor Mobility in Myofibroblast Differentiation.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Lymphatic Dysfunction, Leukotrienes, and Lymphedema.Annual review of physiology · 2018Review
- Regulation of life span by the gut microbiota in the short-lived African turquoise killifish.eLife · 2017Article
- Changes in the Laryngeal Mucosa After Thyroid Surgery: A Rat Model.In vivo (Athens, Greece)Article
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although surgery and radiation are beneficial for treating cancer, they can also lead to malfunctions of the lymphatic system such as secondary lymphedema. This abnormality of the lymphatic system is characterized by severe swelling, adipogenesis, inflammation, and fibrosis in the lymphedematous region. Moreover, the proliferation of fibrotic tissue in the lymphedematous region generates edema that is no longer spontaneously reversible. No treatment for fibrosis has been validated in patients with lymphedema. In our efforts to develop a therapeutic agent for lymphedema fibrosis, we used a newly established mouse hind limb model. Previous studies have demonstrated that hyaluronic acid accumulates in the lymphedematous region. Thus, we challenged mice with of hyaluronidase (HYAL), with the aim of reducing fibrogenesis. After subcutaneous injections in the lymphedematous mouse leg every two days, the volume of lymphedema had reduced significantly by 7 days post-operation. Histochemical analysis indicated that collagen accumulation and myofibroblast differentiation were decreased in epidermal tissues after HYAL injection. Moreover, it was associated with upregulation of interferon-gamma, increased numbers of Th1 cells, and downregulation of interleukin-4 and interleukin-6 in the lymphedematous region and spleen. These results indicate that hydrolysis of hyaluronic acid can boost an anti-fibrotic immune response in the mouse lymphedema model.
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