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Chymase as a Possible Therapeutic Target for Amelioration of Non-Alcoholic Steatohepatitis
The development and progression of non-alcoholic steatohepatitis (NASH) are linked to oxidative stress, inflammation, and fibrosis of the liver. Chymase, a chymotrypsin-like enzyme produced in mast cells, has various enzymatic actions. These actions include activation of angiotensin II, matrix metal...
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| Published in: | International journal of molecular sciences 2020-10, Vol.21 (20), p.7543 |
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| creator | Takai, Shinji Jin, Denan |
| description | The development and progression of non-alcoholic steatohepatitis (NASH) are linked to oxidative stress, inflammation, and fibrosis of the liver. Chymase, a chymotrypsin-like enzyme produced in mast cells, has various enzymatic actions. These actions include activation of angiotensin II, matrix metalloproteinase (MMP)-9, and transforming growth factor (TGF)-β, which are associated with oxidative stress, inflammation, and fibrosis, respectively. Augmentation of chymase activity in the liver has been reported in various NASH models. Generation of hepatic angiotensin II and related oxidative stress is upregulated in NASH but attenuated by treatment with a chymase inhibitor. Additionally, increases in MMP-9 and accumulation of inflammatory cells are observed in NASH but are decreased by chymase inhibitor administration. TGF-β and collagen I upregulation in NASH is also attenuated by chymase inhibition. These results in experimental NASH models demonstrate that a chymase inhibitor can effectively ameliorate NASH via the reduction of oxidative stress, inflammation, and fibrosis. Thus, chymase may be a therapeutic target for amelioration of NASH. |
| doi_str_mv | 10.3390/ijms21207543 |
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Chymase, a chymotrypsin-like enzyme produced in mast cells, has various enzymatic actions. These actions include activation of angiotensin II, matrix metalloproteinase (MMP)-9, and transforming growth factor (TGF)-β, which are associated with oxidative stress, inflammation, and fibrosis, respectively. Augmentation of chymase activity in the liver has been reported in various NASH models. Generation of hepatic angiotensin II and related oxidative stress is upregulated in NASH but attenuated by treatment with a chymase inhibitor. Additionally, increases in MMP-9 and accumulation of inflammatory cells are observed in NASH but are decreased by chymase inhibitor administration. TGF-β and collagen I upregulation in NASH is also attenuated by chymase inhibition. These results in experimental NASH models demonstrate that a chymase inhibitor can effectively ameliorate NASH via the reduction of oxidative stress, inflammation, and fibrosis. Thus, chymase may be a therapeutic target for amelioration of NASH.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms21207543</identifier><identifier>PMID: 33066113</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Angiotensin ; Angiotensin II ; Animals ; Blood pressure ; Chymase ; Chymases - antagonists & inhibitors ; Chymases - metabolism ; Chymotrypsin ; Collagen (type I) ; Enzyme Inhibitors - pharmacology ; Enzyme Inhibitors - therapeutic use ; Enzymes ; Fibrosis ; Gelatinase B ; Gene expression ; Growth factors ; Hepatitis ; Humans ; Hypertension ; Inflammation ; inhibitor ; Inhibitors ; Liver ; Liver - drug effects ; Liver - enzymology ; Liver diseases ; Mast cells ; Matrix metalloproteinase ; Matrix metalloproteinases ; Metabolic syndrome ; Metalloproteinase ; Neutrophils ; Non-alcoholic Fatty Liver Disease - drug therapy ; Non-alcoholic Fatty Liver Disease - metabolism ; non-alcoholic steatohepatitis ; Oxidative stress ; Peptides ; Plasma ; Pulmonary fibrosis ; Review ; Small intestine ; Therapeutic applications</subject><ispartof>International journal of molecular sciences, 2020-10, Vol.21 (20), p.7543</ispartof><rights>2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-6184a25354e88ca1d59c1604cc20217195e2d6085c9e8b095d389013cb08d39b3</citedby><cites>FETCH-LOGICAL-c478t-6184a25354e88ca1d59c1604cc20217195e2d6085c9e8b095d389013cb08d39b3</cites><orcidid>0000-0003-3963-3983</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2548633068/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2548633068?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33066113$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Takai, Shinji</creatorcontrib><creatorcontrib>Jin, Denan</creatorcontrib><title>Chymase as a Possible Therapeutic Target for Amelioration of Non-Alcoholic Steatohepatitis</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>The development and progression of non-alcoholic steatohepatitis (NASH) are linked to oxidative stress, inflammation, and fibrosis of the liver. Chymase, a chymotrypsin-like enzyme produced in mast cells, has various enzymatic actions. These actions include activation of angiotensin II, matrix metalloproteinase (MMP)-9, and transforming growth factor (TGF)-β, which are associated with oxidative stress, inflammation, and fibrosis, respectively. Augmentation of chymase activity in the liver has been reported in various NASH models. Generation of hepatic angiotensin II and related oxidative stress is upregulated in NASH but attenuated by treatment with a chymase inhibitor. Additionally, increases in MMP-9 and accumulation of inflammatory cells are observed in NASH but are decreased by chymase inhibitor administration. TGF-β and collagen I upregulation in NASH is also attenuated by chymase inhibition. These results in experimental NASH models demonstrate that a chymase inhibitor can effectively ameliorate NASH via the reduction of oxidative stress, inflammation, and fibrosis. Thus, chymase may be a therapeutic target for amelioration of NASH.</description><subject>Angiotensin</subject><subject>Angiotensin II</subject><subject>Animals</subject><subject>Blood pressure</subject><subject>Chymase</subject><subject>Chymases - antagonists & inhibitors</subject><subject>Chymases - metabolism</subject><subject>Chymotrypsin</subject><subject>Collagen (type I)</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Enzyme Inhibitors - therapeutic use</subject><subject>Enzymes</subject><subject>Fibrosis</subject><subject>Gelatinase B</subject><subject>Gene expression</subject><subject>Growth factors</subject><subject>Hepatitis</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Inflammation</subject><subject>inhibitor</subject><subject>Inhibitors</subject><subject>Liver</subject><subject>Liver - drug effects</subject><subject>Liver - enzymology</subject><subject>Liver diseases</subject><subject>Mast cells</subject><subject>Matrix metalloproteinase</subject><subject>Matrix metalloproteinases</subject><subject>Metabolic syndrome</subject><subject>Metalloproteinase</subject><subject>Neutrophils</subject><subject>Non-alcoholic Fatty Liver Disease - drug therapy</subject><subject>Non-alcoholic Fatty Liver Disease - metabolism</subject><subject>non-alcoholic steatohepatitis</subject><subject>Oxidative stress</subject><subject>Peptides</subject><subject>Plasma</subject><subject>Pulmonary fibrosis</subject><subject>Review</subject><subject>Small intestine</subject><subject>Therapeutic applications</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNpdks9rFDEUxwdRbK3ePEvASw-O5vdkLsKyqC0UFVwvXkImebOTJTNZkxmh_71Zty1bTwl5Hz7kve-rqtcEv2esxR_8bsyUUNwIzp5U54RTWmMsm6cn97PqRc47jCmjon1enTGGpSSEnVe_1sPtaDIgk5FB32POvguANgMks4dl9hZtTNrCjPqY0GqE4GMys48Tij36Gqd6FWwcYijgjxnMHAfYl_rs88vqWW9Chld350X18_Onzfqqvvn25Xq9uqktb9RcS6K4oYIJDkpZQ5xoLZGYW0sxJQ1pBVAnsRK2BdXhVjimWkyY7bByrO3YRXV99Lpodnqf_GjSrY7G638PMW21SaWRANqxhtveOWJJx63sFfRQzB0xkhvXseL6eHTtl24EZ2GakwmPpI8rkx_0Nv7RjVAtUaIILu8EKf5eIM969NlCCGaCuGRNuSgY4UwV9O1_6C4uaSqj0lRwJQ8hHah3R8qmEk6C_uEzBOvDAujTBSj4m9MGHuD7xNlf6tqsFQ</recordid><startdate>20201013</startdate><enddate>20201013</enddate><creator>Takai, Shinji</creator><creator>Jin, Denan</creator><general>MDPI AG</general><general>MDPI</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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-3963-3983</orcidid></search><sort><creationdate>20201013</creationdate><title>Chymase as a Possible Therapeutic Target for Amelioration of Non-Alcoholic Steatohepatitis</title><author>Takai, Shinji ; Jin, Denan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-6184a25354e88ca1d59c1604cc20217195e2d6085c9e8b095d389013cb08d39b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Angiotensin</topic><topic>Angiotensin II</topic><topic>Animals</topic><topic>Blood pressure</topic><topic>Chymase</topic><topic>Chymases - antagonists & inhibitors</topic><topic>Chymases - metabolism</topic><topic>Chymotrypsin</topic><topic>Collagen (type I)</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Enzyme Inhibitors - therapeutic use</topic><topic>Enzymes</topic><topic>Fibrosis</topic><topic>Gelatinase B</topic><topic>Gene expression</topic><topic>Growth factors</topic><topic>Hepatitis</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Inflammation</topic><topic>inhibitor</topic><topic>Inhibitors</topic><topic>Liver</topic><topic>Liver - drug effects</topic><topic>Liver - enzymology</topic><topic>Liver diseases</topic><topic>Mast cells</topic><topic>Matrix metalloproteinase</topic><topic>Matrix metalloproteinases</topic><topic>Metabolic syndrome</topic><topic>Metalloproteinase</topic><topic>Neutrophils</topic><topic>Non-alcoholic Fatty Liver Disease - drug therapy</topic><topic>Non-alcoholic Fatty Liver Disease - metabolism</topic><topic>non-alcoholic steatohepatitis</topic><topic>Oxidative stress</topic><topic>Peptides</topic><topic>Plasma</topic><topic>Pulmonary fibrosis</topic><topic>Review</topic><topic>Small intestine</topic><topic>Therapeutic applications</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takai, Shinji</creatorcontrib><creatorcontrib>Jin, Denan</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>ProQuest_Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest_Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content (ProQuest)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takai, Shinji</au><au>Jin, Denan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chymase as a Possible Therapeutic Target for Amelioration of Non-Alcoholic Steatohepatitis</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2020-10-13</date><risdate>2020</risdate><volume>21</volume><issue>20</issue><spage>7543</spage><pages>7543-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>The development and progression of non-alcoholic steatohepatitis (NASH) are linked to oxidative stress, inflammation, and fibrosis of the liver. Chymase, a chymotrypsin-like enzyme produced in mast cells, has various enzymatic actions. These actions include activation of angiotensin II, matrix metalloproteinase (MMP)-9, and transforming growth factor (TGF)-β, which are associated with oxidative stress, inflammation, and fibrosis, respectively. Augmentation of chymase activity in the liver has been reported in various NASH models. Generation of hepatic angiotensin II and related oxidative stress is upregulated in NASH but attenuated by treatment with a chymase inhibitor. Additionally, increases in MMP-9 and accumulation of inflammatory cells are observed in NASH but are decreased by chymase inhibitor administration. TGF-β and collagen I upregulation in NASH is also attenuated by chymase inhibition. These results in experimental NASH models demonstrate that a chymase inhibitor can effectively ameliorate NASH via the reduction of oxidative stress, inflammation, and fibrosis. Thus, chymase may be a therapeutic target for amelioration of NASH.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>33066113</pmid><doi>10.3390/ijms21207543</doi><orcidid>https://orcid.org/0000-0003-3963-3983</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Angiotensin Angiotensin II Animals Blood pressure Chymase Chymases - antagonists & inhibitors Chymases - metabolism Chymotrypsin Collagen (type I) Enzyme Inhibitors - pharmacology Enzyme Inhibitors - therapeutic use Enzymes Fibrosis Gelatinase B Gene expression Growth factors Hepatitis Humans Hypertension Inflammation inhibitor Inhibitors Liver Liver - drug effects Liver - enzymology Liver diseases Mast cells Matrix metalloproteinase Matrix metalloproteinases Metabolic syndrome Metalloproteinase Neutrophils Non-alcoholic Fatty Liver Disease - drug therapy Non-alcoholic Fatty Liver Disease - metabolism non-alcoholic steatohepatitis Oxidative stress Peptides Plasma Pulmonary fibrosis Review Small intestine Therapeutic applications |
| title | Chymase as a Possible Therapeutic Target for Amelioration of Non-Alcoholic Steatohepatitis |
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