Antifibrogenic effect of a deletion variant of hepatocyte growth factor on liver fibrosis in rats
Hepatic fibrosis, which may lead to cirrhosis, is associated with most chronic liver diseases. Current therapies for hepatic fibrosis are, however, generally ineffective. In this report we assessed the efficacy of the treatment of hepatic fibrosis with a naturally occurring deletion variant of hepat...
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Veröffentlicht in: | Hepatology (Baltimore, Md.) Md.), 1996-09, Vol.24 (3), p.636-642 |
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description | Hepatic fibrosis, which may lead to cirrhosis, is associated with most chronic liver diseases. Current therapies for hepatic fibrosis are, however, generally ineffective. In this report we assessed the efficacy of the treatment of hepatic fibrosis with a naturally occurring deletion variant of hepatocyte growth factor (dHGF). The administration of dHGF increased liver weight and suppressed the increase of hepatic collagen content in rats treated with dimethylnitrosamine (DMN) to induce hepatic fibrosis. Furthermore, dHGF exerted its mitogenic and antifibrogenic activities even after the liver fibrosis had been established with DMN. Northern blot analysis showed that dHGF suppressed the increase of messenger RNA (mRNA) levels of procollagen α2(I), αl(III), α1(IV), transforming growth factor β1 (TGF‐β1), desmin (a marker of hepatic lipocytes), and α‐smooth muscle (sm)‐actin (a marker of activated hepatic lipocytes). In addition to suppressing the elevated TGF‐β1, mRNA level in hepatic fibrosis, dHGF had a potent ability to decrease TGF‐β1 mRNA level even in a normal liver. Immunohistochemical analysis revealed that desmin‐positive cells and α‐sm‐actin‐positive cells were increased in the hepatic fibrosis, whereas neither cells were seen in livers of DMN‐treated rats given dHGF. We conclude that dHGF prevents and improves the DMN‐induced hepatic fibrosis in rats by reducing mRNA levels of procollagens and TGF‐β1, by inhibiting an activation of hepatic lipocytes, and by stimulating liver regeneration. dHGF may be useful for and applicable to the treatment of fibrosis in chronic liver diseases. |
doi_str_mv | 10.1002/hep.510240328 |
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Current therapies for hepatic fibrosis are, however, generally ineffective. In this report we assessed the efficacy of the treatment of hepatic fibrosis with a naturally occurring deletion variant of hepatocyte growth factor (dHGF). The administration of dHGF increased liver weight and suppressed the increase of hepatic collagen content in rats treated with dimethylnitrosamine (DMN) to induce hepatic fibrosis. Furthermore, dHGF exerted its mitogenic and antifibrogenic activities even after the liver fibrosis had been established with DMN. Northern blot analysis showed that dHGF suppressed the increase of messenger RNA (mRNA) levels of procollagen α2(I), αl(III), α1(IV), transforming growth factor β1 (TGF‐β1), desmin (a marker of hepatic lipocytes), and α‐smooth muscle (sm)‐actin (a marker of activated hepatic lipocytes). In addition to suppressing the elevated TGF‐β1, mRNA level in hepatic fibrosis, dHGF had a potent ability to decrease TGF‐β1 mRNA level even in a normal liver. Immunohistochemical analysis revealed that desmin‐positive cells and α‐sm‐actin‐positive cells were increased in the hepatic fibrosis, whereas neither cells were seen in livers of DMN‐treated rats given dHGF. We conclude that dHGF prevents and improves the DMN‐induced hepatic fibrosis in rats by reducing mRNA levels of procollagens and TGF‐β1, by inhibiting an activation of hepatic lipocytes, and by stimulating liver regeneration. dHGF may be useful for and applicable to the treatment of fibrosis in chronic liver diseases.</description><identifier>ISSN: 0270-9139</identifier><identifier>EISSN: 1527-3350</identifier><identifier>DOI: 10.1002/hep.510240328</identifier><identifier>PMID: 8781336</identifier><identifier>CODEN: HPTLD9</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Actins - genetics ; Actins - metabolism ; Animals ; Biological and medical sciences ; Collagen - metabolism ; Desmin - genetics ; Desmin - metabolism ; Dimethylnitrosamine ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene Deletion ; Genetic Variation ; Hepatocyte Growth Factor - genetics ; Hepatocyte Growth Factor - pharmacology ; Immunohistochemistry ; Liver - metabolism ; Liver - pathology ; Liver Cirrhosis, Experimental - chemically induced ; Liver Cirrhosis, Experimental - pathology ; Liver Cirrhosis, Experimental - prevention & control ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Medical sciences ; Muscle, Smooth - metabolism ; Organ Size - drug effects ; Other diseases. Semiology ; Procollagen - genetics ; Rats ; Rats, Wistar ; RNA, Messenger - metabolism ; Transforming Growth Factor beta - genetics</subject><ispartof>Hepatology (Baltimore, Md.), 1996-09, Vol.24 (3), p.636-642</ispartof><rights>Copyright © 1996 by the American Association for the Study of Liver Diseases</rights><rights>1996 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4028-85dc08d9dd8ba58e554fb8b022ae925cbb4d032526acbe6abedcae11e8a16ebd3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fhep.510240328$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fhep.510240328$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3225167$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8781336$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yasuda, H</creatorcontrib><creatorcontrib>Imai, E</creatorcontrib><creatorcontrib>Shiota, A</creatorcontrib><creatorcontrib>Fujise, N</creatorcontrib><creatorcontrib>Morinaga, T</creatorcontrib><creatorcontrib>Higashio, K</creatorcontrib><title>Antifibrogenic effect of a deletion variant of hepatocyte growth factor on liver fibrosis in rats</title><title>Hepatology (Baltimore, Md.)</title><addtitle>Hepatology</addtitle><description>Hepatic fibrosis, which may lead to cirrhosis, is associated with most chronic liver diseases. Current therapies for hepatic fibrosis are, however, generally ineffective. In this report we assessed the efficacy of the treatment of hepatic fibrosis with a naturally occurring deletion variant of hepatocyte growth factor (dHGF). The administration of dHGF increased liver weight and suppressed the increase of hepatic collagen content in rats treated with dimethylnitrosamine (DMN) to induce hepatic fibrosis. Furthermore, dHGF exerted its mitogenic and antifibrogenic activities even after the liver fibrosis had been established with DMN. Northern blot analysis showed that dHGF suppressed the increase of messenger RNA (mRNA) levels of procollagen α2(I), αl(III), α1(IV), transforming growth factor β1 (TGF‐β1), desmin (a marker of hepatic lipocytes), and α‐smooth muscle (sm)‐actin (a marker of activated hepatic lipocytes). In addition to suppressing the elevated TGF‐β1, mRNA level in hepatic fibrosis, dHGF had a potent ability to decrease TGF‐β1 mRNA level even in a normal liver. Immunohistochemical analysis revealed that desmin‐positive cells and α‐sm‐actin‐positive cells were increased in the hepatic fibrosis, whereas neither cells were seen in livers of DMN‐treated rats given dHGF. We conclude that dHGF prevents and improves the DMN‐induced hepatic fibrosis in rats by reducing mRNA levels of procollagens and TGF‐β1, by inhibiting an activation of hepatic lipocytes, and by stimulating liver regeneration. dHGF may be useful for and applicable to the treatment of fibrosis in chronic liver diseases.</description><subject>Actins - genetics</subject><subject>Actins - metabolism</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Collagen - metabolism</subject><subject>Desmin - genetics</subject><subject>Desmin - metabolism</subject><subject>Dimethylnitrosamine</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene Deletion</subject><subject>Genetic Variation</subject><subject>Hepatocyte Growth Factor - genetics</subject><subject>Hepatocyte Growth Factor - pharmacology</subject><subject>Immunohistochemistry</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Liver Cirrhosis, Experimental - chemically induced</subject><subject>Liver Cirrhosis, Experimental - pathology</subject><subject>Liver Cirrhosis, Experimental - prevention & control</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Muscle, Smooth - metabolism</subject><subject>Organ Size - drug effects</subject><subject>Other diseases. Semiology</subject><subject>Procollagen - genetics</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>RNA, Messenger - metabolism</subject><subject>Transforming Growth Factor beta - genetics</subject><issn>0270-9139</issn><issn>1527-3350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1996</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kDFPwzAQhS0EKqUwMiJ5YE2xnThxxqoqFKkSDDBHZ_vcGqVJZYdW_feEtiob00l3n9579wi552zMGRNPK9yMJWciY6lQF2TIpSiSNJXskgyZKFhS8rS8JjcxfjHGykyoARmoQvE0zYcEJk3nndehXWLjDUXn0HS0dRSoxRo73zZ0C8FDc9j2btC1Zt8hXYZ2162oA9O1gfZY7bcY6EEs-kh9QwN08ZZcOagj3p3miHw-zz6m82Tx9vI6nSwSkzGhEiWtYcqW1ioNUqGUmdNKMyEASyGN1pntP5QiB6MxB43WAHKOCniO2qYjkhx1TW8fA7pqE_wawr7irPptquqzV-emev7hyG--9RrtmT5V098fT3eIBmoXoDE-nrFUCMnzoseKI7bzNe7_96zms_e_AD_LxoN1</recordid><startdate>199609</startdate><enddate>199609</enddate><creator>Yasuda, H</creator><creator>Imai, E</creator><creator>Shiota, A</creator><creator>Fujise, N</creator><creator>Morinaga, T</creator><creator>Higashio, K</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>199609</creationdate><title>Antifibrogenic effect of a deletion variant of hepatocyte growth factor on liver fibrosis in rats</title><author>Yasuda, H ; Imai, E ; Shiota, A ; Fujise, N ; Morinaga, T ; Higashio, K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4028-85dc08d9dd8ba58e554fb8b022ae925cbb4d032526acbe6abedcae11e8a16ebd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1996</creationdate><topic>Actins - genetics</topic><topic>Actins - metabolism</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Collagen - metabolism</topic><topic>Desmin - genetics</topic><topic>Desmin - metabolism</topic><topic>Dimethylnitrosamine</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gene Deletion</topic><topic>Genetic Variation</topic><topic>Hepatocyte Growth Factor - genetics</topic><topic>Hepatocyte Growth Factor - pharmacology</topic><topic>Immunohistochemistry</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Liver Cirrhosis, Experimental - chemically induced</topic><topic>Liver Cirrhosis, Experimental - pathology</topic><topic>Liver Cirrhosis, Experimental - prevention & control</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Muscle, Smooth - metabolism</topic><topic>Organ Size - drug effects</topic><topic>Other diseases. Semiology</topic><topic>Procollagen - genetics</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>RNA, Messenger - metabolism</topic><topic>Transforming Growth Factor beta - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yasuda, H</creatorcontrib><creatorcontrib>Imai, E</creatorcontrib><creatorcontrib>Shiota, A</creatorcontrib><creatorcontrib>Fujise, N</creatorcontrib><creatorcontrib>Morinaga, T</creatorcontrib><creatorcontrib>Higashio, K</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Hepatology (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yasuda, H</au><au>Imai, E</au><au>Shiota, A</au><au>Fujise, N</au><au>Morinaga, T</au><au>Higashio, K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antifibrogenic effect of a deletion variant of hepatocyte growth factor on liver fibrosis in rats</atitle><jtitle>Hepatology (Baltimore, Md.)</jtitle><addtitle>Hepatology</addtitle><date>1996-09</date><risdate>1996</risdate><volume>24</volume><issue>3</issue><spage>636</spage><epage>642</epage><pages>636-642</pages><issn>0270-9139</issn><eissn>1527-3350</eissn><coden>HPTLD9</coden><abstract>Hepatic fibrosis, which may lead to cirrhosis, is associated with most chronic liver diseases. Current therapies for hepatic fibrosis are, however, generally ineffective. In this report we assessed the efficacy of the treatment of hepatic fibrosis with a naturally occurring deletion variant of hepatocyte growth factor (dHGF). The administration of dHGF increased liver weight and suppressed the increase of hepatic collagen content in rats treated with dimethylnitrosamine (DMN) to induce hepatic fibrosis. Furthermore, dHGF exerted its mitogenic and antifibrogenic activities even after the liver fibrosis had been established with DMN. Northern blot analysis showed that dHGF suppressed the increase of messenger RNA (mRNA) levels of procollagen α2(I), αl(III), α1(IV), transforming growth factor β1 (TGF‐β1), desmin (a marker of hepatic lipocytes), and α‐smooth muscle (sm)‐actin (a marker of activated hepatic lipocytes). In addition to suppressing the elevated TGF‐β1, mRNA level in hepatic fibrosis, dHGF had a potent ability to decrease TGF‐β1 mRNA level even in a normal liver. Immunohistochemical analysis revealed that desmin‐positive cells and α‐sm‐actin‐positive cells were increased in the hepatic fibrosis, whereas neither cells were seen in livers of DMN‐treated rats given dHGF. We conclude that dHGF prevents and improves the DMN‐induced hepatic fibrosis in rats by reducing mRNA levels of procollagens and TGF‐β1, by inhibiting an activation of hepatic lipocytes, and by stimulating liver regeneration. dHGF may be useful for and applicable to the treatment of fibrosis in chronic liver diseases.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>8781336</pmid><doi>10.1002/hep.510240328</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Actins - genetics Actins - metabolism Animals Biological and medical sciences Collagen - metabolism Desmin - genetics Desmin - metabolism Dimethylnitrosamine Gastroenterology. Liver. Pancreas. Abdomen Gene Deletion Genetic Variation Hepatocyte Growth Factor - genetics Hepatocyte Growth Factor - pharmacology Immunohistochemistry Liver - metabolism Liver - pathology Liver Cirrhosis, Experimental - chemically induced Liver Cirrhosis, Experimental - pathology Liver Cirrhosis, Experimental - prevention & control Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Medical sciences Muscle, Smooth - metabolism Organ Size - drug effects Other diseases. Semiology Procollagen - genetics Rats Rats, Wistar RNA, Messenger - metabolism Transforming Growth Factor beta - genetics |
title | Antifibrogenic effect of a deletion variant of hepatocyte growth factor on liver fibrosis in rats |
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