Mutant MMP-9 and HGF gene transfer enhance resolution of CCl4-induced liver fibrosis in rats: role of ASH1 and EZH2 methyltransferases repression
Hepatocyte growth factor (HGF) gene transfer inhibits liver fibrosis by regulating aberrant cellular functions, while mutant matrix metalloproteinase-9 (mMMP-9) enhances matrix degradation by neutralizing the elevated tissue inhibitor of metalloproteinase-1 (TIMP-1). It was shown that ASH1 and EZH2...
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| Veröffentlicht in: | PloS one 2014-11, Vol.9 (11), p.e112384-e112384 |
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| creator | Atta, Hussein El-Rehany, Mahmoud Hammam, Olfat Abdel-Ghany, Hend Ramzy, Maggie Roderfeld, Martin Roeb, Elke Al-Hendy, Ayman Raheim, Salama Abdel Allam, Hatem Marey, Heba |
| description | Hepatocyte growth factor (HGF) gene transfer inhibits liver fibrosis by regulating aberrant cellular functions, while mutant matrix metalloproteinase-9 (mMMP-9) enhances matrix degradation by neutralizing the elevated tissue inhibitor of metalloproteinase-1 (TIMP-1). It was shown that ASH1 and EZH2 methyltransferases are involved in development of liver fibrosis; however, their role in the resolution phase of liver fibrosis has not been investigated. This study evaluated the role of ASH1 and EZH2 in two mechanistically different therapeutic modalities, HGF and mMMP-9 gene transfer in CCl4 induced rat liver fibrosis. Liver fibrosis was induced in rats with twice a week intraperitoneal injection of CCl4 for 8 weeks. Adenovirus vectors encoding mMMP-9 or HGF genes were injected through tail vein at weeks six and seven and were sacrificed one week after the second injection. A healthy animal group was likewise injected with saline to serve as a negative control. Rats treated with mMMP-9 showed significantly lower fibrosis score, less Sirius red stained collagen area, reduced hydroxyproline and ALT concentration, decreased transforming growth factor beta 1 (TGF-β1) mRNA and lower labeling indices of α smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) stained cells compared with HGF- or saline-treated rats. Furthermore, TIMP-1 protein expression in mMMP-9 group was markedly reduced compared with all fibrotic groups. ASH1 and EZH2 protein expression was significantly elevated in fibrotic liver and significantly decreased in mMMP-9- and HGF-treated compared to saline-treated fibrotic livers with further reduction in the mMMP-9 group.
Gene transfer of mMMP-9 and HGF reduced liver fibrosis in rats. ASH1 and EZH2 methyltransferases are significantly reduced in mMMP-9 and HGF treated rats which underlines the central role of these enzymes during fibrogenesis. Future studies should evaluate the role of selective pharmacologic inhibitors of ASH1 and EZH2 in resolution of liver fibrosis. |
| doi_str_mv | 10.1371/journal.pone.0112384 |
| format | Article |
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Gene transfer of mMMP-9 and HGF reduced liver fibrosis in rats. ASH1 and EZH2 methyltransferases are significantly reduced in mMMP-9 and HGF treated rats which underlines the central role of these enzymes during fibrogenesis. Future studies should evaluate the role of selective pharmacologic inhibitors of ASH1 and EZH2 in resolution of liver fibrosis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0112384</identifier><identifier>PMID: 25380300</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aberration ; Actin ; Actins - genetics ; Adenoviridae - genetics ; Animals ; Apoptosis ; Biochemistry ; Carbon Tetrachloride ; Cell growth ; Collagen ; Collagen Type I - genetics ; Enhancer of Zeste Homolog 2 Protein ; Enzyme-Linked Immunosorbent Assay ; Enzymes ; Expression vectors ; Fibrosis ; Gastroenterology ; Gelatinase B ; Gene expression ; Gene transfer ; Gene Transfer Techniques ; Genetic Therapy - methods ; Genetic Vectors - genetics ; Growth factors ; Hepatocyte growth factor ; Hepatocyte Growth Factor - genetics ; Hepatocyte Growth Factor - metabolism ; Hepatology ; HGF gene ; Histone-Lysine N-Methyltransferase - metabolism ; Humans ; Hydroxyproline ; Injection ; Liver ; Liver cirrhosis ; Liver Cirrhosis, Experimental - genetics ; Liver Cirrhosis, Experimental - metabolism ; Liver Cirrhosis, Experimental - therapy ; Male ; Matrix metalloproteinase ; Matrix Metalloproteinase 9 - genetics ; Matrix Metalloproteinase 9 - metabolism ; Medicine ; Medicine and Health Sciences ; Metalloproteinase ; Methyltransferases - metabolism ; mRNA ; Muscle, Smooth ; Muscles ; Mutant Proteins - genetics ; Mutant Proteins - metabolism ; Mutation ; Pharmacology ; Polycomb Repressive Complex 2 - metabolism ; Proliferating cell nuclear antigen ; Proteins ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction ; Rodents ; Saline solutions ; Signal transduction ; Smooth muscle ; Tissue inhibitor of metalloproteinase 1 ; Tissue Inhibitor of Metalloproteinase-1 - metabolism ; Transforming growth factor-b1</subject><ispartof>PloS one, 2014-11, Vol.9 (11), p.e112384-e112384</ispartof><rights>2014 Atta et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Atta et al 2014 Atta et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-598bde634f39d29008d91e068baa0f4b24eb1fd19f51d20e1f1d9eefd9c88f4f3</citedby><cites>FETCH-LOGICAL-c526t-598bde634f39d29008d91e068baa0f4b24eb1fd19f51d20e1f1d9eefd9c88f4f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224431/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4224431/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25380300$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Atta, Hussein</creatorcontrib><creatorcontrib>El-Rehany, Mahmoud</creatorcontrib><creatorcontrib>Hammam, Olfat</creatorcontrib><creatorcontrib>Abdel-Ghany, Hend</creatorcontrib><creatorcontrib>Ramzy, Maggie</creatorcontrib><creatorcontrib>Roderfeld, Martin</creatorcontrib><creatorcontrib>Roeb, Elke</creatorcontrib><creatorcontrib>Al-Hendy, Ayman</creatorcontrib><creatorcontrib>Raheim, Salama Abdel</creatorcontrib><creatorcontrib>Allam, Hatem</creatorcontrib><creatorcontrib>Marey, Heba</creatorcontrib><title>Mutant MMP-9 and HGF gene transfer enhance resolution of CCl4-induced liver fibrosis in rats: role of ASH1 and EZH2 methyltransferases repression</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Hepatocyte growth factor (HGF) gene transfer inhibits liver fibrosis by regulating aberrant cellular functions, while mutant matrix metalloproteinase-9 (mMMP-9) enhances matrix degradation by neutralizing the elevated tissue inhibitor of metalloproteinase-1 (TIMP-1). It was shown that ASH1 and EZH2 methyltransferases are involved in development of liver fibrosis; however, their role in the resolution phase of liver fibrosis has not been investigated. This study evaluated the role of ASH1 and EZH2 in two mechanistically different therapeutic modalities, HGF and mMMP-9 gene transfer in CCl4 induced rat liver fibrosis. Liver fibrosis was induced in rats with twice a week intraperitoneal injection of CCl4 for 8 weeks. Adenovirus vectors encoding mMMP-9 or HGF genes were injected through tail vein at weeks six and seven and were sacrificed one week after the second injection. A healthy animal group was likewise injected with saline to serve as a negative control. Rats treated with mMMP-9 showed significantly lower fibrosis score, less Sirius red stained collagen area, reduced hydroxyproline and ALT concentration, decreased transforming growth factor beta 1 (TGF-β1) mRNA and lower labeling indices of α smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) stained cells compared with HGF- or saline-treated rats. Furthermore, TIMP-1 protein expression in mMMP-9 group was markedly reduced compared with all fibrotic groups. ASH1 and EZH2 protein expression was significantly elevated in fibrotic liver and significantly decreased in mMMP-9- and HGF-treated compared to saline-treated fibrotic livers with further reduction in the mMMP-9 group.
Gene transfer of mMMP-9 and HGF reduced liver fibrosis in rats. ASH1 and EZH2 methyltransferases are significantly reduced in mMMP-9 and HGF treated rats which underlines the central role of these enzymes during fibrogenesis. Future studies should evaluate the role of selective pharmacologic inhibitors of ASH1 and EZH2 in resolution of liver fibrosis.</description><subject>Aberration</subject><subject>Actin</subject><subject>Actins - genetics</subject><subject>Adenoviridae - genetics</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Biochemistry</subject><subject>Carbon Tetrachloride</subject><subject>Cell growth</subject><subject>Collagen</subject><subject>Collagen Type I - genetics</subject><subject>Enhancer of Zeste Homolog 2 Protein</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Enzymes</subject><subject>Expression vectors</subject><subject>Fibrosis</subject><subject>Gastroenterology</subject><subject>Gelatinase B</subject><subject>Gene expression</subject><subject>Gene transfer</subject><subject>Gene Transfer Techniques</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors - genetics</subject><subject>Growth factors</subject><subject>Hepatocyte growth factor</subject><subject>Hepatocyte Growth Factor - genetics</subject><subject>Hepatocyte Growth Factor - metabolism</subject><subject>Hepatology</subject><subject>HGF gene</subject><subject>Histone-Lysine N-Methyltransferase - metabolism</subject><subject>Humans</subject><subject>Hydroxyproline</subject><subject>Injection</subject><subject>Liver</subject><subject>Liver cirrhosis</subject><subject>Liver Cirrhosis, Experimental - genetics</subject><subject>Liver Cirrhosis, Experimental - metabolism</subject><subject>Liver Cirrhosis, Experimental - therapy</subject><subject>Male</subject><subject>Matrix metalloproteinase</subject><subject>Matrix Metalloproteinase 9 - genetics</subject><subject>Matrix Metalloproteinase 9 - metabolism</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Metalloproteinase</subject><subject>Methyltransferases - metabolism</subject><subject>mRNA</subject><subject>Muscle, Smooth</subject><subject>Muscles</subject><subject>Mutant Proteins - genetics</subject><subject>Mutant Proteins - metabolism</subject><subject>Mutation</subject><subject>Pharmacology</subject><subject>Polycomb Repressive Complex 2 - metabolism</subject><subject>Proliferating cell nuclear antigen</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Rodents</subject><subject>Saline solutions</subject><subject>Signal transduction</subject><subject>Smooth muscle</subject><subject>Tissue inhibitor of metalloproteinase 1</subject><subject>Tissue Inhibitor of Metalloproteinase-1 - metabolism</subject><subject>Transforming growth factor-b1</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNptks1uEzEUhUcIREvhDRBYYsNmgv9mYrNAqqK2qdQKJGDDxvLY18lEjh3smUp9DN4Y569qEStf2ed8vtc-VfWW4AlhU_JpFccUtJ9sYoAJJoQywZ9Vp0QyWrcUs-eP6pPqVc4rjBsm2vZldUJLgRnGp9Wf23HQYUC3t99qiXSwaH51iRYQAA1Jh-wgIQhLHQygBDn6cehjQNGh2czzug92NGCR7--K0PVdirnPqA8o6SF_Ril62IrPv8_Jjn7xa07RGoblvT_ydYZc2JuCz4X9unrhtM_w5rCeVT8vL37M5vXN16vr2flNbRraDnUjRWehZdwxaanEWFhJALei0xo73lEOHXGWSNcQSzEQR6wEcFYaIVxxnVXv99yNj1kdXjMr0lIiKGV8WhTXe4WNeqU2qV_rdK-i7tVuI6aF0mnojQfVdA0R3dSJKWNc0K4zVgtueNtIQ7HBhfXlcNvYrcEaCGV8_wT69CT0S7WId4pTyjkjBfDxAEjx9wh5UOs-G_BeB4jjrm_ayFbQbd8f_pH-fzq-V5nyZzmBe2iGYLVN2NGltglTh4QV27vHgzyYjpFifwF_68-3</recordid><startdate>20141107</startdate><enddate>20141107</enddate><creator>Atta, Hussein</creator><creator>El-Rehany, Mahmoud</creator><creator>Hammam, Olfat</creator><creator>Abdel-Ghany, Hend</creator><creator>Ramzy, Maggie</creator><creator>Roderfeld, Martin</creator><creator>Roeb, Elke</creator><creator>Al-Hendy, Ayman</creator><creator>Raheim, Salama Abdel</creator><creator>Allam, Hatem</creator><creator>Marey, Heba</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20141107</creationdate><title>Mutant MMP-9 and HGF gene transfer enhance resolution of CCl4-induced liver fibrosis in rats: role of ASH1 and EZH2 methyltransferases repression</title><author>Atta, Hussein ; El-Rehany, Mahmoud ; Hammam, Olfat ; Abdel-Ghany, Hend ; Ramzy, Maggie ; Roderfeld, Martin ; Roeb, Elke ; Al-Hendy, Ayman ; Raheim, Salama Abdel ; Allam, Hatem ; Marey, Heba</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-598bde634f39d29008d91e068baa0f4b24eb1fd19f51d20e1f1d9eefd9c88f4f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Aberration</topic><topic>Actin</topic><topic>Actins - 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metabolism</topic><topic>Transforming growth factor-b1</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Atta, Hussein</creatorcontrib><creatorcontrib>El-Rehany, Mahmoud</creatorcontrib><creatorcontrib>Hammam, Olfat</creatorcontrib><creatorcontrib>Abdel-Ghany, Hend</creatorcontrib><creatorcontrib>Ramzy, Maggie</creatorcontrib><creatorcontrib>Roderfeld, Martin</creatorcontrib><creatorcontrib>Roeb, Elke</creatorcontrib><creatorcontrib>Al-Hendy, Ayman</creatorcontrib><creatorcontrib>Raheim, Salama Abdel</creatorcontrib><creatorcontrib>Allam, Hatem</creatorcontrib><creatorcontrib>Marey, Heba</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection (ProQuest)</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Atta, Hussein</au><au>El-Rehany, Mahmoud</au><au>Hammam, Olfat</au><au>Abdel-Ghany, Hend</au><au>Ramzy, Maggie</au><au>Roderfeld, Martin</au><au>Roeb, Elke</au><au>Al-Hendy, Ayman</au><au>Raheim, Salama Abdel</au><au>Allam, Hatem</au><au>Marey, Heba</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mutant MMP-9 and HGF gene transfer enhance resolution of CCl4-induced liver fibrosis in rats: role of ASH1 and EZH2 methyltransferases repression</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-11-07</date><risdate>2014</risdate><volume>9</volume><issue>11</issue><spage>e112384</spage><epage>e112384</epage><pages>e112384-e112384</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Hepatocyte growth factor (HGF) gene transfer inhibits liver fibrosis by regulating aberrant cellular functions, while mutant matrix metalloproteinase-9 (mMMP-9) enhances matrix degradation by neutralizing the elevated tissue inhibitor of metalloproteinase-1 (TIMP-1). It was shown that ASH1 and EZH2 methyltransferases are involved in development of liver fibrosis; however, their role in the resolution phase of liver fibrosis has not been investigated. This study evaluated the role of ASH1 and EZH2 in two mechanistically different therapeutic modalities, HGF and mMMP-9 gene transfer in CCl4 induced rat liver fibrosis. Liver fibrosis was induced in rats with twice a week intraperitoneal injection of CCl4 for 8 weeks. Adenovirus vectors encoding mMMP-9 or HGF genes were injected through tail vein at weeks six and seven and were sacrificed one week after the second injection. A healthy animal group was likewise injected with saline to serve as a negative control. Rats treated with mMMP-9 showed significantly lower fibrosis score, less Sirius red stained collagen area, reduced hydroxyproline and ALT concentration, decreased transforming growth factor beta 1 (TGF-β1) mRNA and lower labeling indices of α smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) stained cells compared with HGF- or saline-treated rats. Furthermore, TIMP-1 protein expression in mMMP-9 group was markedly reduced compared with all fibrotic groups. ASH1 and EZH2 protein expression was significantly elevated in fibrotic liver and significantly decreased in mMMP-9- and HGF-treated compared to saline-treated fibrotic livers with further reduction in the mMMP-9 group.
Gene transfer of mMMP-9 and HGF reduced liver fibrosis in rats. ASH1 and EZH2 methyltransferases are significantly reduced in mMMP-9 and HGF treated rats which underlines the central role of these enzymes during fibrogenesis. Future studies should evaluate the role of selective pharmacologic inhibitors of ASH1 and EZH2 in resolution of liver fibrosis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25380300</pmid><doi>10.1371/journal.pone.0112384</doi><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-11, Vol.9 (11), p.e112384-e112384 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1621822347 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Aberration Actin Actins - genetics Adenoviridae - genetics Animals Apoptosis Biochemistry Carbon Tetrachloride Cell growth Collagen Collagen Type I - genetics Enhancer of Zeste Homolog 2 Protein Enzyme-Linked Immunosorbent Assay Enzymes Expression vectors Fibrosis Gastroenterology Gelatinase B Gene expression Gene transfer Gene Transfer Techniques Genetic Therapy - methods Genetic Vectors - genetics Growth factors Hepatocyte growth factor Hepatocyte Growth Factor - genetics Hepatocyte Growth Factor - metabolism Hepatology HGF gene Histone-Lysine N-Methyltransferase - metabolism Humans Hydroxyproline Injection Liver Liver cirrhosis Liver Cirrhosis, Experimental - genetics Liver Cirrhosis, Experimental - metabolism Liver Cirrhosis, Experimental - therapy Male Matrix metalloproteinase Matrix Metalloproteinase 9 - genetics Matrix Metalloproteinase 9 - metabolism Medicine Medicine and Health Sciences Metalloproteinase Methyltransferases - metabolism mRNA Muscle, Smooth Muscles Mutant Proteins - genetics Mutant Proteins - metabolism Mutation Pharmacology Polycomb Repressive Complex 2 - metabolism Proliferating cell nuclear antigen Proteins Rats Rats, Wistar Reverse Transcriptase Polymerase Chain Reaction Rodents Saline solutions Signal transduction Smooth muscle Tissue inhibitor of metalloproteinase 1 Tissue Inhibitor of Metalloproteinase-1 - metabolism Transforming growth factor-b1 |
| title | Mutant MMP-9 and HGF gene transfer enhance resolution of CCl4-induced liver fibrosis in rats: role of ASH1 and EZH2 methyltransferases repression |
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