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CD133-Src-TAZ signaling stimulates ductal fibrosis following DDC diet-induced liver injury
- Title
- CD133-Src-TAZ signaling stimulates ductal fibrosis following DDC diet-induced liver injury
- Authors
- Oh H.T.; Heo W.; Yoo G.D.; Kim K.M.; Hwang J.-H.; Hwang E.S.; Ko J.; Ko Y.-G.; Hong J.-H.
- Ewha Authors
- 황은숙
- SCOPUS Author ID
- 황은숙
![scopus](/images/layout/icon2.png)
- Issue Date
- 2022
- Journal Title
- Journal of Cellular Physiology
- ISSN
- 0021-9541
- Citation
- Journal of Cellular Physiology vol. 237, no. 12, pp. 4504 - 4516
- Keywords
- bile ducts; CD133; liver fibrosis; organoids; Src; TAZ
- Publisher
- John Wiley and Sons Inc
- Indexed
- SCIE; SCOPUS
![scopus](/images/layout/scopus2.gif)
- Document Type
- Article
- 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.
- DOI
- 10.1002/jcp.30899
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
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