Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 황은숙 | * |
dc.date.accessioned | 2023-01-06T16:31:14Z | - |
dc.date.available | 2023-01-06T16:31:14Z | - |
dc.date.issued | 2022 | * |
dc.identifier.issn | 0021-9541 | * |
dc.identifier.other | OAK-32704 | * |
dc.identifier.uri | https://dspace.ewha.ac.kr/handle/2015.oak/263151 | - |
dc.description.abstract | Chronic liver injury follows inflammation and liver fibrosis; however, the molecular mechanism underlying fibrosis has not been fully elucidated. In this study, the role of ductal WW domain-containing transcription regulator 1 (WWTR1)/transcriptional coactivator with PDZ-binding motif (TAZ) was investigated after liver injury. Ductal TAZ-knockout (DKO) mice showed decreased liver fibrosis following a Diethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate (DDC) diet compared to wild-type (WT) mice, as evidenced by decreased expression levels of fibrosis inducers, including connective tissue growth factor (Ctgf)/cellular communication network factor 2 (CCN2), cysteine-rich angiogenic inducer 61 (Cyr61/CCN1), and transforming growth factor beta 1 (Tgfb1), in DKO mice. Similarly, TAZ-knockout (KO) cholangiocyte organoids showed decreased expression of fibrosis inducers. Additionally, the culture supernatant of TAZ-KO cholangiocyte organoids decreased the fibrogenic gene expression in liver stellate cells. Further studies revealed that prominin 1 (PROM1/CD133) stimulated TAZ for fibrosis. After the administration of DDC diet, fibrosis was decreased in CD133-KO (CD133-KO) mice compared to that in WT mice. Similarly, CD133-KO cholangiocyte organoids showed decreased Ctgf, Cyr61, and Tgfb1 expression levels compared to WT cholangiocyte organoids. Mechanistically, CD133 stabilized TAZ via Src activation. Inhibition of Src decreased TAZ levels. Similarly, CD133-knockdown HCT116 cells showed decreased TAZ levels, but reintroduction of active Src recovered the TAZ levels. Taken together, our results suggest that TAZ facilitates liver fibrosis after a DDC diet via the CD133-Src-TAZ axis. © 2022 Wiley Periodicals LLC. | * |
dc.language | English | * |
dc.publisher | John Wiley and Sons Inc | * |
dc.subject | bile ducts | * |
dc.subject | CD133 | * |
dc.subject | liver fibrosis | * |
dc.subject | organoids | * |
dc.subject | Src | * |
dc.subject | TAZ | * |
dc.title | CD133-Src-TAZ signaling stimulates ductal fibrosis following DDC diet-induced liver injury | * |
dc.type | Article | * |
dc.relation.issue | 12 | * |
dc.relation.volume | 237 | * |
dc.relation.index | SCIE | * |
dc.relation.index | SCOPUS | * |
dc.relation.startpage | 4504 | * |
dc.relation.lastpage | 4516 | * |
dc.relation.journaltitle | Journal of Cellular Physiology | * |
dc.identifier.doi | 10.1002/jcp.30899 | * |
dc.identifier.scopusid | 2-s2.0-85139964768 | * |
dc.author.google | Oh H.T. | * |
dc.author.google | Heo W. | * |
dc.author.google | Yoo G.D. | * |
dc.author.google | Kim K.M. | * |
dc.author.google | Hwang J.-H. | * |
dc.author.google | Hwang E.S. | * |
dc.author.google | Ko J. | * |
dc.author.google | Ko Y.-G. | * |
dc.author.google | Hong J.-H. | * |
dc.contributor.scopusid | 황은숙(8688011100) | * |
dc.date.modifydate | 20240123102458 | * |