Hydrolysis of Hyaluronic Acid in Lymphedematous Tissue Alleviates Fibrogenesis via TH1 Cell-Mediated Cytokine Expression
Identifieur interne : 000511 ( Main/Exploration ); précédent : 000510; suivant : 000512Hydrolysis of Hyaluronic Acid in Lymphedematous Tissue Alleviates Fibrogenesis via TH1 Cell-Mediated Cytokine Expression
Auteurs : Sungrae Cho [Corée du Sud] ; Kangsan Roh [Corée du Sud] ; Jaehyun Park [Corée du Sud] ; Yong Seok Park [Corée du Sud] ; Minji Lee [Corée du Sud] ; Seungchan Cho [Corée du Sud] ; Eui-Joon Kil [Corée du Sud] ; Mun-Ju Cho [Corée du Sud] ; Jeong Su Oh [Corée du Sud] ; Hee-Seong Byun [Corée du Sud] ; Sang-Ho Cho [Corée du Sud] ; Kyewon Park [Corée du Sud] ; Hee Kang [Corée du Sud] ; Jinmo Koo [Corée du Sud] ; Chang-Hwan Yeom [Corée du Sud] ; Sukchan Lee [Corée du Sud]Source :
- Scientific Reports [ 2045-2322 ] ; 2017.
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.
Url:
DOI: 10.1038/s41598-017-00085-z
PubMed: 28232732
PubMed Central: 5428353
Affiliations:
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wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2181 989X</institution-id><institution-id institution-id-type="GRID">grid.264381.a</institution-id><institution>Department of Genetic Engineering,</institution><institution>Sungkyunkwan University,</institution></institution-wrap>Suwon, 16419 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Suwon</wicri:regionArea></affiliation></author><author><name sortKey="Roh, Kangsan" sort="Roh, Kangsan" uniqKey="Roh K" first="Kangsan" last="Roh">Kangsan Roh</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2181 989X</institution-id><institution-id institution-id-type="GRID">grid.264381.a</institution-id><institution>Department of Genetic Engineering,</institution><institution>Sungkyunkwan University,</institution></institution-wrap>Suwon, 16419 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Suwon</wicri:regionArea></affiliation></author><author><name sortKey="Park, Jaehyun" sort="Park, Jaehyun" uniqKey="Park J" first="Jaehyun" last="Park">Jaehyun Park</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2181 989X</institution-id><institution-id institution-id-type="GRID">grid.264381.a</institution-id><institution>Department of Genetic Engineering,</institution><institution>Sungkyunkwan University,</institution></institution-wrap>Suwon, 16419 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Suwon</wicri:regionArea></affiliation></author><author><name sortKey="Park, Yong Seok" sort="Park, Yong Seok" uniqKey="Park Y" first="Yong Seok" last="Park">Yong Seok Park</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2181 989X</institution-id><institution-id institution-id-type="GRID">grid.264381.a</institution-id><institution>Department of Genetic Engineering,</institution><institution>Sungkyunkwan University,</institution></institution-wrap>Suwon, 16419 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Suwon</wicri:regionArea></affiliation></author><author><name sortKey="Lee, Minji" sort="Lee, Minji" uniqKey="Lee M" first="Minji" last="Lee">Minji Lee</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2181 989X</institution-id><institution-id institution-id-type="GRID">grid.264381.a</institution-id><institution>Department of Genetic Engineering,</institution><institution>Sungkyunkwan University,</institution></institution-wrap>Suwon, 16419 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Suwon</wicri:regionArea></affiliation></author><author><name sortKey="Cho, Seungchan" sort="Cho, Seungchan" uniqKey="Cho S" first="Seungchan" last="Cho">Seungchan Cho</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2181 989X</institution-id><institution-id institution-id-type="GRID">grid.264381.a</institution-id><institution>Department of Genetic Engineering,</institution><institution>Sungkyunkwan University,</institution></institution-wrap>Suwon, 16419 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Suwon</wicri:regionArea></affiliation></author><author><name sortKey="Kil, Eui Joon" sort="Kil, Eui Joon" uniqKey="Kil E" first="Eui-Joon" last="Kil">Eui-Joon Kil</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2181 989X</institution-id><institution-id 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Jeong Su" uniqKey="Oh J" first="Jeong Su" last="Oh">Jeong Su Oh</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2181 989X</institution-id><institution-id institution-id-type="GRID">grid.264381.a</institution-id><institution>Department of Genetic Engineering,</institution><institution>Sungkyunkwan University,</institution></institution-wrap>Suwon, 16419 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Suwon</wicri:regionArea></affiliation></author><author><name sortKey="Byun, Hee Seong" sort="Byun, Hee Seong" uniqKey="Byun H" first="Hee-Seong" last="Byun">Hee-Seong Byun</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2181 989X</institution-id><institution-id institution-id-type="GRID">grid.264381.a</institution-id><institution>Department of Genetic Engineering,</institution><institution>Sungkyunkwan University,</institution></institution-wrap>Suwon, 16419 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Suwon</wicri:regionArea></affiliation></author><author><name sortKey="Cho, Sang Ho" sort="Cho, Sang Ho" uniqKey="Cho S" first="Sang-Ho" last="Cho">Sang-Ho Cho</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2181 989X</institution-id><institution-id institution-id-type="GRID">grid.264381.a</institution-id><institution>Department of Genetic Engineering,</institution><institution>Sungkyunkwan University,</institution></institution-wrap>Suwon, 16419 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Suwon</wicri:regionArea></affiliation></author><author><name sortKey="Park, Kyewon" sort="Park, Kyewon" uniqKey="Park K" first="Kyewon" last="Park">Kyewon Park</name><affiliation wicri:level="1"><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2181 989X</institution-id><institution-id institution-id-type="GRID">grid.264381.a</institution-id><institution>Department of Food Science and Biotechnology,</institution><institution>Sungkyunkwan University,</institution></institution-wrap>Suwon, 16419 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Suwon</wicri:regionArea></affiliation></author><author><name sortKey="Kang, Hee" sort="Kang, Hee" uniqKey="Kang H" first="Hee" last="Kang">Hee Kang</name><affiliation wicri:level="1"><nlm:aff id="Aff3">Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyunghee University, Yongin, 17104 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyunghee University, Yongin</wicri:regionArea><wicri:noRegion>Yongin</wicri:noRegion></affiliation></author><author><name sortKey="Koo, Jinmo" sort="Koo, Jinmo" uniqKey="Koo J" first="Jinmo" last="Koo">Jinmo Koo</name><affiliation wicri:level="1"><nlm:aff id="Aff4">Natural Products Research Department, Gyeonggi Institute of Science & Technology, Suwon, 16229 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Natural Products Research Department, Gyeonggi Institute of Science & Technology, Suwon</wicri:regionArea><wicri:noRegion>Suwon</wicri:noRegion></affiliation></author><author><name sortKey="Yeom, Chang Hwan" sort="Yeom, Chang Hwan" uniqKey="Yeom C" first="Chang-Hwan" last="Yeom">Chang-Hwan Yeom</name><affiliation wicri:level="3"><nlm:aff id="Aff5">U-Cell Clinic, Seoul, 06605 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>U-Cell Clinic, Seoul</wicri:regionArea><placeName><settlement type="city">Séoul</settlement><region type="capital">Région capitale de Séoul</region></placeName></affiliation></author><author><name sortKey="Lee, Sukchan" sort="Lee, Sukchan" uniqKey="Lee S" first="Sukchan" last="Lee">Sukchan Lee</name><affiliation wicri:level="1"><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2181 989X</institution-id><institution-id institution-id-type="GRID">grid.264381.a</institution-id><institution>Department of Genetic Engineering,</institution><institution>Sungkyunkwan University,</institution></institution-wrap>Suwon, 16419 Republic of Korea</nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Suwon</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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. 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first="Sungrae" last="Cho">Sungrae Cho</name></noRegion><name sortKey="Byun, Hee Seong" sort="Byun, Hee Seong" uniqKey="Byun H" first="Hee-Seong" last="Byun">Hee-Seong Byun</name><name sortKey="Cho, Mun Ju" sort="Cho, Mun Ju" uniqKey="Cho M" first="Mun-Ju" last="Cho">Mun-Ju Cho</name><name sortKey="Cho, Sang Ho" sort="Cho, Sang Ho" uniqKey="Cho S" first="Sang-Ho" last="Cho">Sang-Ho Cho</name><name sortKey="Cho, Seungchan" sort="Cho, Seungchan" uniqKey="Cho S" first="Seungchan" last="Cho">Seungchan Cho</name><name sortKey="Kang, Hee" sort="Kang, Hee" uniqKey="Kang H" first="Hee" last="Kang">Hee Kang</name><name sortKey="Kil, Eui Joon" sort="Kil, Eui Joon" uniqKey="Kil E" first="Eui-Joon" last="Kil">Eui-Joon Kil</name><name sortKey="Koo, Jinmo" sort="Koo, Jinmo" uniqKey="Koo J" first="Jinmo" last="Koo">Jinmo Koo</name><name sortKey="Lee, Minji" sort="Lee, Minji" uniqKey="Lee M" first="Minji" last="Lee">Minji Lee</name><name sortKey="Lee, Sukchan" sort="Lee, Sukchan" uniqKey="Lee S" first="Sukchan" last="Lee">Sukchan Lee</name><name sortKey="Oh, Jeong Su" sort="Oh, Jeong Su" uniqKey="Oh J" first="Jeong Su" last="Oh">Jeong Su Oh</name><name sortKey="Park, Jaehyun" sort="Park, Jaehyun" uniqKey="Park J" first="Jaehyun" last="Park">Jaehyun Park</name><name sortKey="Park, Kyewon" sort="Park, Kyewon" uniqKey="Park K" first="Kyewon" last="Park">Kyewon Park</name><name sortKey="Park, Yong Seok" sort="Park, Yong Seok" uniqKey="Park Y" first="Yong Seok" last="Park">Yong Seok Park</name><name sortKey="Roh, Kangsan" sort="Roh, Kangsan" uniqKey="Roh K" first="Kangsan" last="Roh">Kangsan Roh</name><name sortKey="Yeom, Chang Hwan" sort="Yeom, Chang Hwan" uniqKey="Yeom C" first="Chang-Hwan" last="Yeom">Chang-Hwan Yeom</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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