miR-133b Regulation of Connective Tissue Growth Factor: A Novel Mechanism in Liver Pathology
miRNAs are involved in liver regeneration, and their expression is dysregulated in hepatocellular carcinoma (HCC). Connective tissue growth factor (CTGF), a direct target of miR-133b, is crucial in the ductular reaction (DR)/oval cell (OC) response for generating new hepatocyte lineages during liver...
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| Veröffentlicht in: | The American journal of pathology 2016-05, Vol.186 (5), p.1092-1102 |
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| creator | Gjymishka, Altin Pi, Liya Oh, Seh-Hoon Jorgensen, Marda Liu, Chen Protopapadakis, Yianni Patel, Ashnee Petersen, Bryon E |
| description | miRNAs are involved in liver regeneration, and their expression is dysregulated in hepatocellular carcinoma (HCC). Connective tissue growth factor (CTGF), a direct target of miR-133b, is crucial in the ductular reaction (DR)/oval cell (OC) response for generating new hepatocyte lineages during liver injury in the context of hepatotoxin-inhibited hepatocyte proliferation. Herein, we investigate whether miR-133b regulation of CTGF influences HCC cell proliferation and migration, and DR/OC response. We analyzed miR-133b expression and found it to be down-regulated in HCC patient samples and induced in the rat DR/OC activation model of 2-acetylaminofluorene with partial hepatectomy. Furthermore, overexpression of miR-133b via adenoviral system in vitro led to decreased CTGF expression and reduced proliferation and Transwell migration of both HepG2 HCC cells and WBF-344 rat OCs. In vivo, overexpression of miR-133b in DR/OC activation models of 2-acetylaminofluorene with partial hepatectomy in rats, and 3,5-diethoxycarbonyl-1,4-dihydrocollidine in mice, led to down-regulation of CTGF expression and OC proliferation. Collectively, these results show that miR-133b regulation of CTGF is a novel mechanism critical for the proliferation and migration of HCC cells and OC response. |
| doi_str_mv | 10.1016/j.ajpath.2015.12.022 |
| format | Article |
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Connective tissue growth factor (CTGF), a direct target of miR-133b, is crucial in the ductular reaction (DR)/oval cell (OC) response for generating new hepatocyte lineages during liver injury in the context of hepatotoxin-inhibited hepatocyte proliferation. Herein, we investigate whether miR-133b regulation of CTGF influences HCC cell proliferation and migration, and DR/OC response. We analyzed miR-133b expression and found it to be down-regulated in HCC patient samples and induced in the rat DR/OC activation model of 2-acetylaminofluorene with partial hepatectomy. Furthermore, overexpression of miR-133b via adenoviral system in vitro led to decreased CTGF expression and reduced proliferation and Transwell migration of both HepG2 HCC cells and WBF-344 rat OCs. In vivo, overexpression of miR-133b in DR/OC activation models of 2-acetylaminofluorene with partial hepatectomy in rats, and 3,5-diethoxycarbonyl-1,4-dihydrocollidine in mice, led to down-regulation of CTGF expression and OC proliferation. Collectively, these results show that miR-133b regulation of CTGF is a novel mechanism critical for the proliferation and migration of HCC cells and OC response.</description><identifier>ISSN: 0002-9440</identifier><identifier>EISSN: 1525-2191</identifier><identifier>DOI: 10.1016/j.ajpath.2015.12.022</identifier><identifier>PMID: 26945106</identifier><language>eng</language><publisher>United States: American Society for Investigative Pathology</publisher><subject>2-Acetylaminofluorene - pharmacology ; Adenoviridae - genetics ; Aged ; Animals ; Carcinogens - pharmacology ; Carcinoma, Hepatocellular - physiopathology ; Cell Movement - physiology ; Cell Proliferation - physiology ; Connective Tissue Growth Factor - metabolism ; Disease Models, Animal ; Down-Regulation - physiology ; Female ; Genetic Vectors ; HEK293 Cells ; Hep G2 Cells ; Humans ; Liver Neoplasms - physiopathology ; Male ; Mice ; MicroRNAs - metabolism ; MicroRNAs - physiology ; Middle Aged ; Rats ; Short Communication ; Transfection</subject><ispartof>The American journal of pathology, 2016-05, Vol.186 (5), p.1092-1102</ispartof><rights>Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.</rights><rights>2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. 2016 American Society for Investigative Pathology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861761/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4861761/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26945106$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gjymishka, Altin</creatorcontrib><creatorcontrib>Pi, Liya</creatorcontrib><creatorcontrib>Oh, Seh-Hoon</creatorcontrib><creatorcontrib>Jorgensen, Marda</creatorcontrib><creatorcontrib>Liu, Chen</creatorcontrib><creatorcontrib>Protopapadakis, Yianni</creatorcontrib><creatorcontrib>Patel, Ashnee</creatorcontrib><creatorcontrib>Petersen, Bryon E</creatorcontrib><title>miR-133b Regulation of Connective Tissue Growth Factor: A Novel Mechanism in Liver Pathology</title><title>The American journal of pathology</title><addtitle>Am J Pathol</addtitle><description>miRNAs are involved in liver regeneration, and their expression is dysregulated in hepatocellular carcinoma (HCC). Connective tissue growth factor (CTGF), a direct target of miR-133b, is crucial in the ductular reaction (DR)/oval cell (OC) response for generating new hepatocyte lineages during liver injury in the context of hepatotoxin-inhibited hepatocyte proliferation. Herein, we investigate whether miR-133b regulation of CTGF influences HCC cell proliferation and migration, and DR/OC response. We analyzed miR-133b expression and found it to be down-regulated in HCC patient samples and induced in the rat DR/OC activation model of 2-acetylaminofluorene with partial hepatectomy. Furthermore, overexpression of miR-133b via adenoviral system in vitro led to decreased CTGF expression and reduced proliferation and Transwell migration of both HepG2 HCC cells and WBF-344 rat OCs. In vivo, overexpression of miR-133b in DR/OC activation models of 2-acetylaminofluorene with partial hepatectomy in rats, and 3,5-diethoxycarbonyl-1,4-dihydrocollidine in mice, led to down-regulation of CTGF expression and OC proliferation. Collectively, these results show that miR-133b regulation of CTGF is a novel mechanism critical for the proliferation and migration of HCC cells and OC response.</description><subject>2-Acetylaminofluorene - pharmacology</subject><subject>Adenoviridae - genetics</subject><subject>Aged</subject><subject>Animals</subject><subject>Carcinogens - pharmacology</subject><subject>Carcinoma, Hepatocellular - physiopathology</subject><subject>Cell Movement - physiology</subject><subject>Cell Proliferation - physiology</subject><subject>Connective Tissue Growth Factor - metabolism</subject><subject>Disease Models, Animal</subject><subject>Down-Regulation - physiology</subject><subject>Female</subject><subject>Genetic Vectors</subject><subject>HEK293 Cells</subject><subject>Hep G2 Cells</subject><subject>Humans</subject><subject>Liver Neoplasms - physiopathology</subject><subject>Male</subject><subject>Mice</subject><subject>MicroRNAs - metabolism</subject><subject>MicroRNAs - physiology</subject><subject>Middle Aged</subject><subject>Rats</subject><subject>Short Communication</subject><subject>Transfection</subject><issn>0002-9440</issn><issn>1525-2191</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkNtKw0AQhhdRbK2-gci-QOLsbnabeCGUYqtQD5R6J4TdZNJsSbIhh0rf3ogH9GoY5v8_PoaQSwY-A6aud77e1brLfQ5M-oz7wPkRGTPJpcdZxI7JGAC4FwUBjMhZ2-6GVYkQTsmIqyiQDNSYvJV27TEhDF3jti90Z11FXUbnrqow6ewe6ca2bY902bj3LqcLnXSuuaEz-uT2WNBHTHJd2baktqKrId_Ql8HKFW57OCcnmS5avPieE_K6uNvM773V8_JhPlt5NVeq83hoIJHIFSplpoCYpcmnHorQiAgUF1NhglRKybRRIgAZahmYlGMmhIRQTMjtF7fuTYlpglXX6CKuG1vq5hA7beP_l8rm8dbt4yBUbKrYALj6C_ht_vxJfACmAGx-</recordid><startdate>201605</startdate><enddate>201605</enddate><creator>Gjymishka, Altin</creator><creator>Pi, Liya</creator><creator>Oh, Seh-Hoon</creator><creator>Jorgensen, Marda</creator><creator>Liu, Chen</creator><creator>Protopapadakis, Yianni</creator><creator>Patel, Ashnee</creator><creator>Petersen, Bryon E</creator><general>American Society for Investigative Pathology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>5PM</scope></search><sort><creationdate>201605</creationdate><title>miR-133b Regulation of Connective Tissue Growth Factor: A Novel Mechanism in Liver Pathology</title><author>Gjymishka, Altin ; Pi, Liya ; Oh, Seh-Hoon ; Jorgensen, Marda ; Liu, Chen ; Protopapadakis, Yianni ; Patel, Ashnee ; Petersen, Bryon E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p266t-28b0c5e26e66b70eefdc4510e38b39062373b4d5551ab634058a54bd2ef335083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>2-Acetylaminofluorene - pharmacology</topic><topic>Adenoviridae - genetics</topic><topic>Aged</topic><topic>Animals</topic><topic>Carcinogens - pharmacology</topic><topic>Carcinoma, Hepatocellular - physiopathology</topic><topic>Cell Movement - physiology</topic><topic>Cell Proliferation - physiology</topic><topic>Connective Tissue Growth Factor - metabolism</topic><topic>Disease Models, Animal</topic><topic>Down-Regulation - physiology</topic><topic>Female</topic><topic>Genetic Vectors</topic><topic>HEK293 Cells</topic><topic>Hep G2 Cells</topic><topic>Humans</topic><topic>Liver Neoplasms - physiopathology</topic><topic>Male</topic><topic>Mice</topic><topic>MicroRNAs - metabolism</topic><topic>MicroRNAs - physiology</topic><topic>Middle Aged</topic><topic>Rats</topic><topic>Short Communication</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gjymishka, Altin</creatorcontrib><creatorcontrib>Pi, Liya</creatorcontrib><creatorcontrib>Oh, Seh-Hoon</creatorcontrib><creatorcontrib>Jorgensen, Marda</creatorcontrib><creatorcontrib>Liu, Chen</creatorcontrib><creatorcontrib>Protopapadakis, Yianni</creatorcontrib><creatorcontrib>Patel, Ashnee</creatorcontrib><creatorcontrib>Petersen, Bryon E</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The American journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gjymishka, Altin</au><au>Pi, Liya</au><au>Oh, Seh-Hoon</au><au>Jorgensen, Marda</au><au>Liu, Chen</au><au>Protopapadakis, Yianni</au><au>Patel, Ashnee</au><au>Petersen, Bryon E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>miR-133b Regulation of Connective Tissue Growth Factor: A Novel Mechanism in Liver Pathology</atitle><jtitle>The American journal of pathology</jtitle><addtitle>Am J Pathol</addtitle><date>2016-05</date><risdate>2016</risdate><volume>186</volume><issue>5</issue><spage>1092</spage><epage>1102</epage><pages>1092-1102</pages><issn>0002-9440</issn><eissn>1525-2191</eissn><abstract>miRNAs are involved in liver regeneration, and their expression is dysregulated in hepatocellular carcinoma (HCC). Connective tissue growth factor (CTGF), a direct target of miR-133b, is crucial in the ductular reaction (DR)/oval cell (OC) response for generating new hepatocyte lineages during liver injury in the context of hepatotoxin-inhibited hepatocyte proliferation. Herein, we investigate whether miR-133b regulation of CTGF influences HCC cell proliferation and migration, and DR/OC response. We analyzed miR-133b expression and found it to be down-regulated in HCC patient samples and induced in the rat DR/OC activation model of 2-acetylaminofluorene with partial hepatectomy. Furthermore, overexpression of miR-133b via adenoviral system in vitro led to decreased CTGF expression and reduced proliferation and Transwell migration of both HepG2 HCC cells and WBF-344 rat OCs. In vivo, overexpression of miR-133b in DR/OC activation models of 2-acetylaminofluorene with partial hepatectomy in rats, and 3,5-diethoxycarbonyl-1,4-dihydrocollidine in mice, led to down-regulation of CTGF expression and OC proliferation. Collectively, these results show that miR-133b regulation of CTGF is a novel mechanism critical for the proliferation and migration of HCC cells and OC response.</abstract><cop>United States</cop><pub>American Society for Investigative Pathology</pub><pmid>26945106</pmid><doi>10.1016/j.ajpath.2015.12.022</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 2-Acetylaminofluorene - pharmacology Adenoviridae - genetics Aged Animals Carcinogens - pharmacology Carcinoma, Hepatocellular - physiopathology Cell Movement - physiology Cell Proliferation - physiology Connective Tissue Growth Factor - metabolism Disease Models, Animal Down-Regulation - physiology Female Genetic Vectors HEK293 Cells Hep G2 Cells Humans Liver Neoplasms - physiopathology Male Mice MicroRNAs - metabolism MicroRNAs - physiology Middle Aged Rats Short Communication Transfection |
| title | miR-133b Regulation of Connective Tissue Growth Factor: A Novel Mechanism in Liver Pathology |
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