دورية أكاديمية
Cholest-4,6-Dien-3-One Promote Epithelial-To-Mesenchymal Transition (EMT) in Biliary Tree Stem/Progenitor Cell Cultures In Vitro
| العنوان: | Cholest-4,6-Dien-3-One Promote Epithelial-To-Mesenchymal Transition (EMT) in Biliary Tree Stem/Progenitor Cell Cultures In Vitro |
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| المؤلفون: | Nevi L., Costantini D., Safarikia S., Di Matteo S., Melandro F., Berloco P. B., Cardinale V. |
| المساهمون: | L. Nevi, D. Costantini, S. Safarikia, S. Di Matteo, F. Melandro, P.B. Berloco, V. Cardinale |
| بيانات النشر: | MDPI |
| سنة النشر: | 2019 |
| المجموعة: | The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| مصطلحات موضوعية: | biliary tree stem/progenitor cells (BTSCs), BMP pathway, epithelial-to-mesenchymal transition (EMT), primary sclerosing cholangitis (PSC), senescence, SHH pathway, telomerase, Biliary Tract, Cell Differentiation, Cell Proliferation, Cells, Cultured, Cellular Senescence, Cholestenone, Epithelial-Mesenchymal Transition, Histone Deacetylase 6, Human, Interleukin-6, Signal Transduction, Stem Cell, Tissue Donors, Settore BIO/11 - Biologia Molecolare, Settore MED/12 - Gastroenterologia |
| الوصف: | Human biliary tree stem/progenitor cells (hBTSCs), reside in peribiliary glands, are mainly stimulated by primary sclerosing cholangitis (PSC) and cholangiocarcinoma. In these pathologies, hBTSCs displayed epithelial-to-mesenchymal transition (EMT), senescence characteristics, and impaired differentiation. Here, we investigated the effects of cholest-4,6-dien-3-one, an oxysterol involved in cholangiopathies, on hBTSCs biology. hBTSCs were isolated from donor organs, cultured in self-renewal control conditions, differentiated in mature cholangiocytes by specifically tailored medium, or exposed for 10 days to concentration of cholest-4,6-dien-3-one (0.14 mM). Viability, proliferation, senescence, EMT genes expression, telomerase activity, interleukin 6 (IL6) secretion, differentiation capacity, and HDAC6 gene expression were analyzed. Although the effect of cholest-4,6-dien-3-one was not detected on hBTSCs viability, we found a significant increase in cell proliferation, senescence, and IL6 secretion. Interestingly, cholest-4.6-dien-3-one impaired differentiation in mature cholangiocytes and, simultaneously, induced the EMT markers, significantly reduced the telomerase activity, and induced HDAC6 gene expression. Moreover, cholest-4,6-dien-3-one enhanced bone morphogenic protein 4 (Bmp-4) and sonic hedgehog (Shh) pathways in hBTSCs. The same pathways activated by human recombinant proteins induced the expression of EMT markers in hBTSCs. In conclusion, we demonstrated that chronic exposition of cholest-4,6-dien-3-one induced cell proliferation, EMT markers, and senescence in hBTSC, and also impaired the differentiation in mature cholangiocytes. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/31731674; info:eu-repo/semantics/altIdentifier/wos/WOS:000502266700141; volume:8; issue:11; firstpage:1; lastpage:21; numberofpages:21; journal:CELLS; http://hdl.handle.net/2434/794933Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85088609305 |
| DOI: | 10.3390/cells8111443 |
| الإتاحة: | https://doi.org/10.3390/cells8111443Test http://hdl.handle.net/2434/794933Test |
| حقوق: | info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.37305914 |
| قاعدة البيانات: | BASE |
| DOI: | 10.3390/cells8111443 |
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