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Selective deletion of hepatocyte platelet-derived growth factor receptor α and development of liver fibrosis in mice

DC Field Value Language
dc.contributor.author김자경-
dc.contributor.author이관식-
dc.contributor.author이정일-
dc.contributor.author이현웅-
dc.contributor.author임범진-
dc.date.accessioned2019-01-15T17:07:54Z-
dc.date.available2019-01-15T17:07:54Z-
dc.date.issued2018-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/166824-
dc.description.abstractBACKGROUND: Platelet-derived growth factor receptor α (PDGFRα) expression is increased in activated hepatic stellate cells (HSCs) in cirrhotic liver, while normal hepatocytes express PDGFRα at a negligible level. However, cancerous hepatocytes may show upregulation of PDGFRα, and hepatocellular carcinoma is preceded by chronic liver injury. The role of PDGFRα in non-cancerous hepatocytes and liver fibrosis is unclear. We hypothesized that upon liver injury, PDGFRα in insulted hepatocytes contributes to liver fibrosis by facilitating intercellular crosstalk between hepatocytes and HSCs. METHODS: Hepatocytes were isolated from normal and thioacetamide (TAA)-induced cirrhotic livers for assessment of PDGFRα expression. Conditional knock-out (KO) C57BL/6 mice, in which PDGFRα was selectively deleted in hepatocytes, were generated. Liver fibrosis was induced by injecting TAA for 8 weeks. Hep3B cells were transfected with a small interfering RNA (siRNA) (PDGFRα or control) and co-cultured with LX2 cells. RESULTS: PDGFRα expression was increased in hepatocytes from fibrotic livers compared to normal livers. Conditional PDGFRα KO mice had attenuated TAA-induced liver fibrosis with decreased HSC activation and proliferation. Immunoblot analyses revealed decreased expression of phospho-p44/42 MAPK in TAA-treated KO mice; these mice also showed almost complete suppression of the upregulation of mouse double minute 2. Although KO mice exhibited increased expression of transforming growth factor (TGF)-β and Smad2/3, this was compensated for by increased expression of inhibitory Smad7. LX2 cells co-cultured with PDGFRα siRNA-infected Hep3B cells showed decreased PDGFRα, α smooth muscle actin, collagen α1(I), TGFβ, and Smad2/3 expression. LX2/PDGFRα-deleted hepatocyte co-culture medium showed decreased PDGF-BB and PDGF-CC levels. CONCLUSIONS: Deletion of PDGFRα in hepatocytes attenuated the upregulation of PDGFRα in HSCs after TAA treatment, resulting in decreased liver fibrosis and HSC activation. This suggests that in the event of chronic liver injury, PDGFRα in hepatocytes plays an important role in liver fibrosis by affecting PDGFRα expression in HSCs.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherBioMed Central-
dc.relation.isPartOfCELL COMMUNICATION AND SIGNALING-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleSelective deletion of hepatocyte platelet-derived growth factor receptor α and development of liver fibrosis in mice-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.googleauthorBeom Jin Lim-
dc.contributor.googleauthorWoon-Kyu Lee-
dc.contributor.googleauthorHyun Woong Lee-
dc.contributor.googleauthorKwan Sik Lee-
dc.contributor.googleauthorJa Kyung Kim-
dc.contributor.googleauthorHye Young Chang-
dc.contributor.googleauthorJung Il Lee-
dc.identifier.doi10.1186/s12964-018-0306-2-
dc.contributor.localIdA00852-
dc.contributor.localIdA02666-
dc.contributor.localIdA02666-
dc.contributor.localIdA03122-
dc.contributor.localIdA03122-
dc.contributor.localIdA03292-
dc.contributor.localIdA03292-
dc.contributor.localIdA03363-
dc.contributor.localIdA03363-
dc.relation.journalcodeJ00480-
dc.identifier.eissn1478-811X-
dc.identifier.pmid30509307-
dc.subject.keywordHepatic stellate cell-
dc.subject.keywordHepatocyte-
dc.subject.keywordLiver cirrhosis-
dc.subject.keywordLiver fibrosis-
dc.subject.keywordPlatelet-derived growth factor receptor α-
dc.contributor.alternativeNameKim, Ja Kyung-
dc.contributor.affiliatedAuthor김자경-
dc.contributor.affiliatedAuthor이관식-
dc.contributor.affiliatedAuthor이관식-
dc.contributor.affiliatedAuthor이정일-
dc.contributor.affiliatedAuthor이정일-
dc.contributor.affiliatedAuthor이현웅-
dc.contributor.affiliatedAuthor이현웅-
dc.contributor.affiliatedAuthor임범진-
dc.contributor.affiliatedAuthor임범진-
dc.citation.volume16-
dc.citation.number1-
dc.citation.startPage93-
dc.identifier.bibliographicCitationCELL COMMUNICATION AND SIGNALING, Vol.16(1) : 93, 2018-
dc.identifier.rimsid58199-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers

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