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Cho S, Roh K, Park J, Park YS, Lee M, Cho S, Kil EJ, Cho MJ, Oh JS, Byun HS, Cho SH, Park K, Kang H, Koo J, Yeom CH, Lee S, et al.
Scientific reports. Date of publication 2017 Feb 24;volume 7(1):35.
1. Sci Rep. 2017 Feb 24;7(1):35. doi: 10.1038/s41598-017-00085-z. Hydrolysis of Hyaluronic Acid in Lymphedematous Tissue Alleviates Fibrogenesis via TH1 Cell-Mediated Cytokine Expression. Cho S(1), Roh K(1), Park J(1), Park YS(1), Lee M(1), Cho S(1), Kil EJ(1), Cho MJ(1), Oh JS(1), Byun HS(1), Cho SH(1), Park K(2), Kang H(3), Koo J(4), Yeom CH(5), Lee S(6). Author information: (1)Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea. (2)Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, 16419, Republic of Korea. (3)Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyunghee University, Yongin, 17104, Republic of Korea. (4)Natural Products Research Department, Gyeonggi Institute of Science & Technology, Suwon, 16229, Republic of Korea. (5)U-Cell Clinic, Seoul, 06605, Republic of Korea. (6)Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea. cell4u@skku.edu. 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. DOI: 10.1038/s41598-017-00085-z PMCID: PMC5428353 PMID: 28232732 [Indexed for MEDLINE]
Appears in following Topics:
Lymphedema - Treatment and Emerging Strategies for Prevention