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Hepatocyte growth factor (HGF), HGF activator, and c-Met in synovial tissues in rheumatoid arthritis and osteoarthritis

OBJECTIVE: Hepatocyte growth factor (HGF) is a multifunctional polypeptide that has been implicated in cancer growth, tissue development, and wound repair. Its actions are dependent on activation by HGF activator (HGFA) and its binding to a specific HGF receptor (c-Met). We examined the role of HGF,...

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Published in:Journal of rheumatology 2001-08, Vol.28 (8), p.1772-1778
Main Authors: NAGASHIMA, Masakazu, HASEGAWA, Jun, KATO, Ko, YAMAZAKI, Junji, NISHIGAI, Keiko, ISHIWATA, Toshiyuki, ASANO, Goro, YOSHINO, Shinichi
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container_end_page 1778
container_issue 8
container_start_page 1772
container_title Journal of rheumatology
container_volume 28
creator NAGASHIMA, Masakazu
HASEGAWA, Jun
KATO, Ko
YAMAZAKI, Junji
NISHIGAI, Keiko
ISHIWATA, Toshiyuki
ASANO, Goro
YOSHINO, Shinichi
description OBJECTIVE: Hepatocyte growth factor (HGF) is a multifunctional polypeptide that has been implicated in cancer growth, tissue development, and wound repair. Its actions are dependent on activation by HGF activator (HGFA) and its binding to a specific HGF receptor (c-Met). We examined the role of HGF, HGFA, and c-Met in synovial tissues in rheumatoid arthritis (RA) and osteoarthritis (OA), and their localization and mRNA expression. METHODS: Immunohistochemical staining, Western blotting, RT-PCR, and in situ hybridization (ISH) for HGF, HGFA, and c-Met were performed on synovial tissue specimens from 10 patients with RA and 4 with OA, and 2 healthy controls. RESULTS: Immunohistochemical staining revealed that HGFA and c-Met were strongly expressed in fibroblasts, macrophages, endothelial cells, and synovial lining cells. HGF was expressed only faintly in macrophages and fibroblasts, and not at all in the endothelial cells of RA and OA synovial tissue. HGFA was detected near 73 and 34 kDa on Western blot analysis, corresponding to inactive and active HGFA, respectively. RT-PCR showed HGF, HGFA, and c-Met mRNA in RA, OA, and control synovial tissue. ISH and immunohistochemistry revealed mRNA expression for HGF, HGFA, and c-Met in the cell types mentioned above. CONCLUSION: HGFA, HGF, and c-Met mRNA are expressed in synovial tissue in RA and OA, and HGF is activated by HGFA and binds to c-Met on endothelial cells, inducing angiogenesis.
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Its actions are dependent on activation by HGF activator (HGFA) and its binding to a specific HGF receptor (c-Met). We examined the role of HGF, HGFA, and c-Met in synovial tissues in rheumatoid arthritis (RA) and osteoarthritis (OA), and their localization and mRNA expression. METHODS: Immunohistochemical staining, Western blotting, RT-PCR, and in situ hybridization (ISH) for HGF, HGFA, and c-Met were performed on synovial tissue specimens from 10 patients with RA and 4 with OA, and 2 healthy controls. RESULTS: Immunohistochemical staining revealed that HGFA and c-Met were strongly expressed in fibroblasts, macrophages, endothelial cells, and synovial lining cells. HGF was expressed only faintly in macrophages and fibroblasts, and not at all in the endothelial cells of RA and OA synovial tissue. HGFA was detected near 73 and 34 kDa on Western blot analysis, corresponding to inactive and active HGFA, respectively. RT-PCR showed HGF, HGFA, and c-Met mRNA in RA, OA, and control synovial tissue. ISH and immunohistochemistry revealed mRNA expression for HGF, HGFA, and c-Met in the cell types mentioned above. CONCLUSION: HGFA, HGF, and c-Met mRNA are expressed in synovial tissue in RA and OA, and HGF is activated by HGFA and binds to c-Met on endothelial cells, inducing angiogenesis.</description><identifier>ISSN: 0315-162X</identifier><identifier>EISSN: 1499-2752</identifier><identifier>PMID: 11508578</identifier><identifier>CODEN: JRHUA9</identifier><language>eng</language><publisher>Toronto, ON: The Journal of Rheumatology</publisher><subject>Arthritis, Rheumatoid - metabolism ; Biological and medical sciences ; Blotting, Western ; Diseases of the osteoarticular system ; Hepatocyte Growth Factor - analysis ; Hepatocyte Growth Factor - genetics ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Inflammatory joint diseases ; Medical sciences ; Neovascularization, Pathologic - metabolism ; Osteoarthritis - metabolism ; Proto-Oncogene Proteins c-met - analysis ; Proto-Oncogene Proteins c-met - genetics ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - analysis ; Serine Endopeptidases - analysis ; Serine Endopeptidases - genetics ; Synovial Membrane - chemistry ; Synovial Membrane - physiology</subject><ispartof>Journal of rheumatology, 2001-08, Vol.28 (8), p.1772-1778</ispartof><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=14061643$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11508578$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>NAGASHIMA, Masakazu</creatorcontrib><creatorcontrib>HASEGAWA, Jun</creatorcontrib><creatorcontrib>KATO, Ko</creatorcontrib><creatorcontrib>YAMAZAKI, Junji</creatorcontrib><creatorcontrib>NISHIGAI, Keiko</creatorcontrib><creatorcontrib>ISHIWATA, Toshiyuki</creatorcontrib><creatorcontrib>ASANO, Goro</creatorcontrib><creatorcontrib>YOSHINO, Shinichi</creatorcontrib><title>Hepatocyte growth factor (HGF), HGF activator, and c-Met in synovial tissues in rheumatoid arthritis and osteoarthritis</title><title>Journal of rheumatology</title><addtitle>J Rheumatol</addtitle><description>OBJECTIVE: Hepatocyte growth factor (HGF) is a multifunctional polypeptide that has been implicated in cancer growth, tissue development, and wound repair. Its actions are dependent on activation by HGF activator (HGFA) and its binding to a specific HGF receptor (c-Met). We examined the role of HGF, HGFA, and c-Met in synovial tissues in rheumatoid arthritis (RA) and osteoarthritis (OA), and their localization and mRNA expression. METHODS: Immunohistochemical staining, Western blotting, RT-PCR, and in situ hybridization (ISH) for HGF, HGFA, and c-Met were performed on synovial tissue specimens from 10 patients with RA and 4 with OA, and 2 healthy controls. RESULTS: Immunohistochemical staining revealed that HGFA and c-Met were strongly expressed in fibroblasts, macrophages, endothelial cells, and synovial lining cells. HGF was expressed only faintly in macrophages and fibroblasts, and not at all in the endothelial cells of RA and OA synovial tissue. HGFA was detected near 73 and 34 kDa on Western blot analysis, corresponding to inactive and active HGFA, respectively. RT-PCR showed HGF, HGFA, and c-Met mRNA in RA, OA, and control synovial tissue. ISH and immunohistochemistry revealed mRNA expression for HGF, HGFA, and c-Met in the cell types mentioned above. CONCLUSION: HGFA, HGF, and c-Met mRNA are expressed in synovial tissue in RA and OA, and HGF is activated by HGFA and binds to c-Met on endothelial cells, inducing angiogenesis.</description><subject>Arthritis, Rheumatoid - metabolism</subject><subject>Biological and medical sciences</subject><subject>Blotting, Western</subject><subject>Diseases of the osteoarticular system</subject><subject>Hepatocyte Growth Factor - analysis</subject><subject>Hepatocyte Growth Factor - genetics</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>In Situ Hybridization</subject><subject>Inflammatory joint diseases</subject><subject>Medical sciences</subject><subject>Neovascularization, Pathologic - metabolism</subject><subject>Osteoarthritis - metabolism</subject><subject>Proto-Oncogene Proteins c-met - analysis</subject><subject>Proto-Oncogene Proteins c-met - genetics</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - analysis</subject><subject>Serine Endopeptidases - analysis</subject><subject>Serine Endopeptidases - genetics</subject><subject>Synovial Membrane - chemistry</subject><subject>Synovial Membrane - physiology</subject><issn>0315-162X</issn><issn>1499-2752</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><recordid>eNpFkNtKAzEQhhdRbK2-guRGUehCstlD9lKKbYWKNwreLdPNpBvZQ02yXfr2Rq32Zgb--eafw0kwZnGeh1GWRKfBmHKWhCyN3kfBhbUflLI0TsV5MGIsoSLJxDgYlrgF15V7h2RjusFVREHpOkPulov5_ZT4SLygd54yUwKtJGX4jI7olth92-001MRpa3u035qpsG88qyUB4yqjfe2nq7MOu3_pMjhTUFu8OuRJ8DZ_fJ0tw9XL4mn2sAqrKBUuTABBpSh5TAUVQjIeZSqJgScSMxDKn4SlYJDnHJUEJhWTMdJ1qSjnsQA-CW5_fbem-_QruqLRtsS6hha73hYZYzRhEfPg9QHs1w3KYmt0A2Zf_L3KAzcHAGwJtTLQltoeuZim_r38OLHSm2rQBgvbQF17W14MwxCJQhQsyyL-BY6Hgco</recordid><startdate>20010801</startdate><enddate>20010801</enddate><creator>NAGASHIMA, Masakazu</creator><creator>HASEGAWA, Jun</creator><creator>KATO, Ko</creator><creator>YAMAZAKI, Junji</creator><creator>NISHIGAI, Keiko</creator><creator>ISHIWATA, Toshiyuki</creator><creator>ASANO, Goro</creator><creator>YOSHINO, Shinichi</creator><general>The Journal of Rheumatology</general><general>Journal of Rheumatology Publishing</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20010801</creationdate><title>Hepatocyte growth factor (HGF), HGF activator, and c-Met in synovial tissues in rheumatoid arthritis and osteoarthritis</title><author>NAGASHIMA, Masakazu ; 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Its actions are dependent on activation by HGF activator (HGFA) and its binding to a specific HGF receptor (c-Met). We examined the role of HGF, HGFA, and c-Met in synovial tissues in rheumatoid arthritis (RA) and osteoarthritis (OA), and their localization and mRNA expression. METHODS: Immunohistochemical staining, Western blotting, RT-PCR, and in situ hybridization (ISH) for HGF, HGFA, and c-Met were performed on synovial tissue specimens from 10 patients with RA and 4 with OA, and 2 healthy controls. RESULTS: Immunohistochemical staining revealed that HGFA and c-Met were strongly expressed in fibroblasts, macrophages, endothelial cells, and synovial lining cells. HGF was expressed only faintly in macrophages and fibroblasts, and not at all in the endothelial cells of RA and OA synovial tissue. HGFA was detected near 73 and 34 kDa on Western blot analysis, corresponding to inactive and active HGFA, respectively. RT-PCR showed HGF, HGFA, and c-Met mRNA in RA, OA, and control synovial tissue. ISH and immunohistochemistry revealed mRNA expression for HGF, HGFA, and c-Met in the cell types mentioned above. CONCLUSION: HGFA, HGF, and c-Met mRNA are expressed in synovial tissue in RA and OA, and HGF is activated by HGFA and binds to c-Met on endothelial cells, inducing angiogenesis.</abstract><cop>Toronto, ON</cop><pub>The Journal of Rheumatology</pub><pmid>11508578</pmid><tpages>7</tpages></addata></record>
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ispartof Journal of rheumatology, 2001-08, Vol.28 (8), p.1772-1778
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source Freely Accessible Journals
subjects Arthritis, Rheumatoid - metabolism
Biological and medical sciences
Blotting, Western
Diseases of the osteoarticular system
Hepatocyte Growth Factor - analysis
Hepatocyte Growth Factor - genetics
Humans
Immunohistochemistry
In Situ Hybridization
Inflammatory joint diseases
Medical sciences
Neovascularization, Pathologic - metabolism
Osteoarthritis - metabolism
Proto-Oncogene Proteins c-met - analysis
Proto-Oncogene Proteins c-met - genetics
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - analysis
Serine Endopeptidases - analysis
Serine Endopeptidases - genetics
Synovial Membrane - chemistry
Synovial Membrane - physiology
title Hepatocyte growth factor (HGF), HGF activator, and c-Met in synovial tissues in rheumatoid arthritis and osteoarthritis
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