Hydrolysis of Hyaluronic Acid in Lymphedematous Tissue Alleviates Fibrogenesis via TH1 Cell-Mediated Cytokine Expression.
Identifieur interne : 000346 ( PubMed/Curation ); précédent : 000345; suivant : 000347Hydrolysis 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.
DOI: 10.1038/s41598-017-00085-z
PubMed: 28232732
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University, Suwon, 16419, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419</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:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419</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:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419</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:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419</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:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419</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:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419</wicri:regionArea></affiliation></author><author><name sortKey="Cho, Mun Ju" sort="Cho, Mun Ju" uniqKey="Cho M" first="Mun-Ju" last="Cho">Mun-Ju Cho</name><affiliation wicri:level="1"><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419</wicri:regionArea></affiliation></author><author><name sortKey="Oh, Jeong Su" sort="Oh, Jeong Su" uniqKey="Oh J" first="Jeong Su" last="Oh">Jeong Su Oh</name><affiliation wicri:level="1"><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419</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:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419</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:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419</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:affiliation>Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, 16419</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:affiliation>Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyunghee University, Yongin, 17104, Republic of Korea.</nlm:affiliation><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, 17104</wicri:regionArea></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:affiliation>Natural Products Research Department, Gyeonggi Institute of Science & Technology, Suwon, 16229, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Natural Products Research Department, Gyeonggi Institute of Science & Technology, Suwon, 16229</wicri:regionArea></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="1"><nlm:affiliation>U-Cell Clinic, Seoul, 06605, Republic of Korea.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>U-Cell Clinic, Seoul, 06605</wicri:regionArea></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:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea. cell4u@skku.edu.</nlm:affiliation><country xml:lang="fr">Corée du Sud</country><wicri:regionArea>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">28232732</PMID><DateCreated><Year>2017</Year><Month>02</Month><Day>24</Day></DateCreated><DateRevised><Year>2017</Year><Month>09</Month><Day>06</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2045-2322</ISSN><JournalIssue CitedMedium="Internet"><Volume>7</Volume><Issue>1</Issue><PubDate><Year>2017</Year><Month>02</Month><Day>24</Day></PubDate></JournalIssue><Title>Scientific reports</Title><ISOAbbreviation>Sci Rep</ISOAbbreviation></Journal><ArticleTitle>Hydrolysis of Hyaluronic Acid in Lymphedematous Tissue Alleviates Fibrogenesis via TH1 Cell-Mediated Cytokine Expression.</ArticleTitle><Pagination><MedlinePgn>35</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/s41598-017-00085-z</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Cho</LastName><ForeName>Sungrae</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Roh</LastName><ForeName>Kangsan</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Park</LastName><ForeName>Jaehyun</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Park</LastName><ForeName>Yong Seok</ForeName><Initials>YS</Initials><AffiliationInfo><Affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Minji</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cho</LastName><ForeName>Seungchan</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kil</LastName><ForeName>Eui-Joon</ForeName><Initials>EJ</Initials><AffiliationInfo><Affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cho</LastName><ForeName>Mun-Ju</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Oh</LastName><ForeName>Jeong Su</ForeName><Initials>JS</Initials><AffiliationInfo><Affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Byun</LastName><ForeName>Hee-Seong</ForeName><Initials>HS</Initials><AffiliationInfo><Affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cho</LastName><ForeName>Sang-Ho</ForeName><Initials>SH</Initials><AffiliationInfo><Affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Park</LastName><ForeName>Kyewon</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kang</LastName><ForeName>Hee</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyunghee University, Yongin, 17104, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Koo</LastName><ForeName>Jinmo</ForeName><Initials>J</Initials><Identifier Source="ORCID">0000-0003-0218-810X</Identifier><AffiliationInfo><Affiliation>Natural Products Research Department, Gyeonggi Institute of Science & Technology, Suwon, 16229, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yeom</LastName><ForeName>Chang-Hwan</ForeName><Initials>CH</Initials><AffiliationInfo><Affiliation>U-Cell Clinic, Seoul, 06605, Republic of Korea.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lee</LastName><ForeName>Sukchan</ForeName><Initials>S</Initials><Identifier Source="ORCID">0000-0002-9964-0176</Identifier><AffiliationInfo><Affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea. cell4u@skku.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>02</Month><Day>24</Day></ArticleDate></Article><MedlineJournalInfo><Country>England</Country><MedlineTA>Sci 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