Hydrolysis of Hyaluronic Acid in Lymphedematous Tissue Alleviates Fibrogenesis via TH1 Cell-Mediated Cytokine Expression.
Identifieur interne : 000346 ( PubMed/Corpus ); précédent : 000345; suivant : 000347Hydrolysis of Hyaluronic Acid in Lymphedematous Tissue Alleviates Fibrogenesis via TH1 Cell-Mediated Cytokine Expression.
Auteurs : 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 LeeSource :
- 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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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Hydrolysis of Hyaluronic Acid in Lymphedematous Tissue Alleviates Fibrogenesis via TH1 Cell-Mediated Cytokine Expression.</title><author><name sortKey="Cho, Sungrae" sort="Cho, Sungrae" uniqKey="Cho S" first="Sungrae" last="Cho">Sungrae Cho</name><affiliation><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Roh, Kangsan" sort="Roh, Kangsan" uniqKey="Roh K" first="Kangsan" last="Roh">Kangsan Roh</name><affiliation><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Park, Jaehyun" sort="Park, Jaehyun" uniqKey="Park J" first="Jaehyun" last="Park">Jaehyun Park</name><affiliation><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></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><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Lee, Minji" sort="Lee, Minji" uniqKey="Lee M" first="Minji" last="Lee">Minji Lee</name><affiliation><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Cho, Seungchan" sort="Cho, Seungchan" uniqKey="Cho S" first="Seungchan" last="Cho">Seungchan Cho</name><affiliation><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></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><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></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><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></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><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></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><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></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><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Park, Kyewon" sort="Park, Kyewon" uniqKey="Park K" first="Kyewon" last="Park">Kyewon Park</name><affiliation><nlm:affiliation>Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Kang, Hee" sort="Kang, Hee" uniqKey="Kang H" first="Hee" last="Kang">Hee Kang</name><affiliation><nlm:affiliation>Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyunghee University, Yongin, 17104, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Koo, Jinmo" sort="Koo, Jinmo" uniqKey="Koo J" first="Jinmo" last="Koo">Jinmo Koo</name><affiliation><nlm:affiliation>Natural Products Research Department, Gyeonggi Institute of Science & Technology, Suwon, 16229, Republic of Korea.</nlm:affiliation></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><nlm:affiliation>U-Cell Clinic, Seoul, 06605, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Lee, Sukchan" sort="Lee, Sukchan" uniqKey="Lee S" first="Sukchan" last="Lee">Sukchan Lee</name><affiliation><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea. cell4u@skku.edu.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:28232732</idno><idno type="pmid">28232732</idno><idno type="doi">10.1038/s41598-017-00085-z</idno><idno type="wicri:Area/PubMed/Corpus">000346</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000346</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Hydrolysis of Hyaluronic Acid in Lymphedematous Tissue Alleviates Fibrogenesis via TH1 Cell-Mediated Cytokine Expression.</title><author><name sortKey="Cho, Sungrae" sort="Cho, Sungrae" uniqKey="Cho S" first="Sungrae" last="Cho">Sungrae Cho</name><affiliation><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Roh, Kangsan" sort="Roh, Kangsan" uniqKey="Roh K" first="Kangsan" last="Roh">Kangsan Roh</name><affiliation><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Park, Jaehyun" sort="Park, Jaehyun" uniqKey="Park J" first="Jaehyun" last="Park">Jaehyun Park</name><affiliation><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></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><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Lee, Minji" sort="Lee, Minji" uniqKey="Lee M" first="Minji" last="Lee">Minji Lee</name><affiliation><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Cho, Seungchan" sort="Cho, Seungchan" uniqKey="Cho S" first="Seungchan" last="Cho">Seungchan Cho</name><affiliation><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></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><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></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><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></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><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></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><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></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><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Park, Kyewon" sort="Park, Kyewon" uniqKey="Park K" first="Kyewon" last="Park">Kyewon Park</name><affiliation><nlm:affiliation>Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon, 16419, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Kang, Hee" sort="Kang, Hee" uniqKey="Kang H" first="Hee" last="Kang">Hee Kang</name><affiliation><nlm:affiliation>Department of Oriental Medical Science, Graduate School of East-West Medical Science, Kyunghee University, Yongin, 17104, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Koo, Jinmo" sort="Koo, Jinmo" uniqKey="Koo J" first="Jinmo" last="Koo">Jinmo Koo</name><affiliation><nlm:affiliation>Natural Products Research Department, Gyeonggi Institute of Science & Technology, Suwon, 16229, Republic of Korea.</nlm:affiliation></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><nlm:affiliation>U-Cell Clinic, Seoul, 06605, Republic of Korea.</nlm:affiliation></affiliation></author><author><name sortKey="Lee, Sukchan" sort="Lee, Sukchan" uniqKey="Lee S" first="Sukchan" last="Lee">Sukchan Lee</name><affiliation><nlm:affiliation>Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea. cell4u@skku.edu.</nlm:affiliation></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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