Hydrolysis of Hyaluronic Acid in Lymphedematous Tissue Alleviates Fibrogenesis via TH1 Cell-Mediated Cytokine Expression
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 lymphedem...
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2017
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oai:doaj.org-article:e293b5158fe14451941c9276c970a26e2021-12-02T12:30:26ZHydrolysis of Hyaluronic Acid in Lymphedematous Tissue Alleviates Fibrogenesis via TH1 Cell-Mediated Cytokine Expression10.1038/s41598-017-00085-z2045-2322https://doaj.org/article/e293b5158fe14451941c9276c970a26e2017-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00085-zhttps://doaj.org/toc/2045-2322Abstract 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.Sungrae ChoKangsan RohJaehyun ParkYong Seok ParkMinji LeeSeungchan ChoEui-Joon KilMun-Ju ChoJeong Su OhHee-Seong ByunSang-Ho ChoKyewon ParkHee KangJinmo KooChang-Hwan YeomSukchan LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017) |
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EN |
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Medicine R Science Q |
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Medicine R Science Q Sungrae Cho Kangsan Roh Jaehyun Park Yong Seok Park Minji Lee Seungchan Cho Eui-Joon Kil Mun-Ju Cho Jeong Su Oh Hee-Seong Byun Sang-Ho Cho Kyewon Park Hee Kang Jinmo Koo Chang-Hwan Yeom Sukchan Lee Hydrolysis of Hyaluronic Acid in Lymphedematous Tissue Alleviates Fibrogenesis via TH1 Cell-Mediated Cytokine Expression |
| description |
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. |
| format |
article |
| author |
Sungrae Cho Kangsan Roh Jaehyun Park Yong Seok Park Minji Lee Seungchan Cho Eui-Joon Kil Mun-Ju Cho Jeong Su Oh Hee-Seong Byun Sang-Ho Cho Kyewon Park Hee Kang Jinmo Koo Chang-Hwan Yeom Sukchan Lee |
| author_facet |
Sungrae Cho Kangsan Roh Jaehyun Park Yong Seok Park Minji Lee Seungchan Cho Eui-Joon Kil Mun-Ju Cho Jeong Su Oh Hee-Seong Byun Sang-Ho Cho Kyewon Park Hee Kang Jinmo Koo Chang-Hwan Yeom Sukchan Lee |
| author_sort |
Sungrae Cho |
| title |
Hydrolysis of Hyaluronic Acid in Lymphedematous Tissue Alleviates Fibrogenesis via TH1 Cell-Mediated Cytokine Expression |
| title_short |
Hydrolysis of Hyaluronic Acid in Lymphedematous Tissue Alleviates Fibrogenesis via TH1 Cell-Mediated Cytokine Expression |
| title_full |
Hydrolysis of Hyaluronic Acid in Lymphedematous Tissue Alleviates Fibrogenesis via TH1 Cell-Mediated Cytokine Expression |
| title_fullStr |
Hydrolysis of Hyaluronic Acid in Lymphedematous Tissue Alleviates Fibrogenesis via TH1 Cell-Mediated Cytokine Expression |
| title_full_unstemmed |
Hydrolysis of Hyaluronic Acid in Lymphedematous Tissue Alleviates Fibrogenesis via TH1 Cell-Mediated Cytokine Expression |
| title_sort |
hydrolysis of hyaluronic acid in lymphedematous tissue alleviates fibrogenesis via th1 cell-mediated cytokine expression |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/e293b5158fe14451941c9276c970a26e |
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