DC Field | Value | Language |
---|---|---|
dc.contributor.author | J Ryu | - |
dc.contributor.author | E Kim | - |
dc.contributor.author | M K Kang | - |
dc.contributor.author | D G Song | - |
dc.contributor.author | E A Shin | - |
dc.contributor.author | H Lee | - |
dc.contributor.author | J W Jung | - |
dc.contributor.author | S H Nam | - |
dc.contributor.author | J E Kim | - |
dc.contributor.author | H J Kim | - |
dc.contributor.author | T Son | - |
dc.contributor.author | Semi Kim | - |
dc.contributor.author | H Y Kim | - |
dc.contributor.author | J W Lee | - |
dc.date.accessioned | 2021-02-26T08:33:13Z | - |
dc.date.available | 2021-02-26T08:33:13Z | - |
dc.date.issued | 2021 | - |
dc.identifier.issn | 0022-3417 | - |
dc.identifier.uri | https://oak.kribb.re.kr/handle/201005/24138 | - |
dc.description.abstract | Nonalcoholic fatty liver disease is a chronic condition involving steatosis, steatohepatitis and fibrosis, and its progression remains unclear. Although the tetraspanin transmembrane 4 L six family member 5 (TM4SF5) is involved in hepatic fibrosis and cancer, its role in nonalcoholic steatohepatitis (NASH) progression is unknown. We investigated the contribution of TM4SF5 to liver pathology using transgenic and KO mice, diet- or drug-treated mice, in vitro primary cells, and in human tissue. TM4SF5-overexpressing mice exhibited nonalcoholic steatosis and NASH in an age-dependent manner. Initially, TM4SF5-positive hepatocytes and liver tissue exhibited lipid accumulation, decreased Sirtuin 1 (SIRT1), increased sterol regulatory-element binding proteins (SREBPs) and inactive STAT3 via suppressor of cytokine signaling (SOCS)1/3 upregulation. In older mice, TM4SF5 promoted inflammatory factor induction, SIRT1 expression and STAT3 activity, but did not change SOCS or SREBP levels, leading to active STAT3-mediated ECM production for NASH progression. A TM4SF5-associated increase in chemokines promoted SIRT1 expression and progression to NASH with fibrosis. Suppression of the chemokine CCL20 reduced immune cell infiltration and ECM production. Liver tissue from high-fat diet- or CCl4-treated mice and human patients exhibited TM4SF5-dependent steatotic or steatohepatitic livers with links between TM4SF5-mediated SIRT1 modulation and SREBP or SOCS/STAT3 signaling axes. TM4SF5-mediated STAT3 activation in fibrotic NASH livers increased collagen I and laminin γ2. Both collagen I α1 and laminin γ2 suppression resulted in reduced SIRT1 and active STAT3, but no change in SREBP1 or SOCS, and abolished CCl4?mediated mouse liver damage. TM4SF5-mediated signaling pathways that involve SIRT1, SREBPs and SOCS/STAT3 promoted progression to NASH. Therefore, TM4SF5 and its downstream effectors may be promising therapeutic targets to treat nonalcoholic fatty liver disease. | - |
dc.publisher | Wiley | - |
dc.title | Differential TM4SF5-mediated SIRT1 modulation and metabolic signaling in nonalcoholic steatohepatitis progression | - |
dc.title.alternative | Differential TM4SF5-mediated SIRT1 modulation and metabolic signaling in nonalcoholic steatohepatitis progression | - |
dc.type | Article | - |
dc.citation.title | Journal of Pathology | - |
dc.citation.number | 0 | - |
dc.citation.endPage | 67 | - |
dc.citation.startPage | 55 | - |
dc.citation.volume | 253 | - |
dc.contributor.affiliatedAuthor | Semi Kim | - |
dc.contributor.alternativeName | 류지혜 | - |
dc.contributor.alternativeName | 김은미 | - |
dc.contributor.alternativeName | 강민경 | - |
dc.contributor.alternativeName | 송대근 | - |
dc.contributor.alternativeName | 신은애 | - |
dc.contributor.alternativeName | 이해송 | - |
dc.contributor.alternativeName | 정재우 | - |
dc.contributor.alternativeName | 남세희 | - |
dc.contributor.alternativeName | 김지언 | - |
dc.contributor.alternativeName | 김혜진 | - |
dc.contributor.alternativeName | 손태권 | - |
dc.contributor.alternativeName | 김세미 | - |
dc.contributor.alternativeName | 김휘영 | - |
dc.contributor.alternativeName | 이정원 | - |
dc.identifier.bibliographicCitation | Journal of Pathology, vol. 253, pp. 55-67 | - |
dc.identifier.doi | 10.1002/path.5548 | - |
dc.subject.keyword | CCL20 | - |
dc.subject.keyword | Laminin γ2 | - |
dc.subject.keyword | NAFLD | - |
dc.subject.keyword | NASH | - |
dc.subject.keyword | Signal transduction | - |
dc.subject.keyword | SIRT1 | - |
dc.subject.keyword | SOCS | - |
dc.subject.keyword | SREBP | - |
dc.subject.keyword | STAT3 | - |
dc.subject.keyword | TM4SF5 | - |
dc.subject.local | CCL20 | - |
dc.subject.local | Laminin γ2 | - |
dc.subject.local | NAFLD | - |
dc.subject.local | NASH | - |
dc.subject.local | Signal transduction | - |
dc.subject.local | Signal trasduction | - |
dc.subject.local | signal transduction | - |
dc.subject.local | SIRT-1 | - |
dc.subject.local | SIRT1 | - |
dc.subject.local | SOCS | - |
dc.subject.local | SREBP | - |
dc.subject.local | SREBPs | - |
dc.subject.local | Signal transducer and activator of transcription 3 (STAT3) | - |
dc.subject.local | Signal transducer and activator of transcription | - |
dc.subject.local | Signal transducer and activator of transcription 3 (Stat3) | - |
dc.subject.local | STAT 3 | - |
dc.subject.local | STAT3 | - |
dc.subject.local | Signal transducer and activator of transcription 3 | - |
dc.subject.local | Stat3 | - |
dc.subject.local | Signal transducer and activator of transcription factor 3 (STAT3) | - |
dc.subject.local | TM4SF5 | - |
dc.description.journalClass | Y | - |
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