دورية أكاديمية
Genetic labeling does not detect epithelial-to-mesenchymal transition of cholangiocytes in liver fibrosis in mice.
العنوان: | Genetic labeling does not detect epithelial-to-mesenchymal transition of cholangiocytes in liver fibrosis in mice. |
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المؤلفون: | Scholten D; Department of Medicine, University of California, San Diego, La Jolla, California, USA., Osterreicher CH, Scholten A, Iwaisako K, Gu G, Brenner DA, Kisseleva T |
المصدر: | Gastroenterology [Gastroenterology] 2010 Sep; Vol. 139 (3), pp. 987-98. Date of Electronic Publication: 2010 Jun 20. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: W.B. Saunders Country of Publication: United States NLM ID: 0374630 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-0012 (Electronic) Linking ISSN: 00165085 NLM ISO Abbreviation: Gastroenterology Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Philadelphia, PA : W.B. Saunders Original Publication: Baltimore. |
مواضيع طبية MeSH: | Cell Transdifferentiation*/genetics , Liver Regeneration*/genetics, Chemical and Drug Induced Liver Injury/*pathology , Epithelial Cells/*pathology , Fibroblasts/*pathology , Liver/*pathology , Liver Cirrhosis/*pathology, Animals ; Bile Ducts/surgery ; Biomarkers/metabolism ; Calcium-Binding Proteins/genetics ; Carbon Tetrachloride ; Cell Lineage ; Chemical and Drug Induced Liver Injury/genetics ; Chemical and Drug Induced Liver Injury/metabolism ; Collagen Type II/genetics ; Crosses, Genetic ; Disease Models, Animal ; Epithelial Cells/metabolism ; Fibroblasts/metabolism ; Genes, Reporter ; Glial Fibrillary Acidic Protein/genetics ; Hepatic Stellate Cells/pathology ; Immunohistochemistry ; Keratin-19/genetics ; Ligation ; Liver/metabolism ; Liver Cirrhosis/genetics ; Liver Cirrhosis/metabolism ; Luminescent Proteins/biosynthesis ; Luminescent Proteins/genetics ; Mice ; Mice, Transgenic ; Promoter Regions, Genetic ; Proteins/genetics ; RNA, Untranslated ; S100 Calcium-Binding Protein A4 ; S100 Proteins |
مستخلص: | Background & Aims: Chronic injury changes the fate of certain cellular populations, inducing epithelial cells to generate fibroblasts by epithelial-to-mesenchymal transition (EMT) and mesenchymal cells to generate epithelial cells by mesenchymal-to-epithelial transition (MET). Although contribution of EMT/MET to embryogenesis, renal fibrosis, and lung fibrosis is well documented, role of EMT/MET in liver fibrosis is unclear. We determined whether cytokeratin-19 positive (K19(+)) cholangiocytes give rise to myofibroblasts (EMT) and/or whether glial fibrillary acidic protein positive (GFAP(+)) hepatic stellate cells (HSCs) can express epithelial markers (MET) in response to experimental liver injury. Methods: EMT was studied with Cre-loxP system to map cell fate of K19(+) cholangiocytes in K19(YFP) or fibroblast-specific protein-1 (FSP-1)(YFP) mice, generated by crossing tamoxifen-inducible K19(CreERT) mice or FSP-1(Cre) mice with Rosa26(f/f-YFP) mice. MET of GFAP(+) HSCs was studied in GFAP(GFP) mice. Mice were subjected to bile duct ligation or CCl(4)-liver injury, and livers were analyzed for expression of mesodermal and epithelial markers. Results: On Cre-loxP recombination, >40% of genetically labeled K19(+) cholangiocytes expressed yellow fluorescent protein (YFP). All mice developed liver fibrosis. However, specific immunostaining of K19(YFP) cholangiocytes showed no expression of EMT markers alpha-smooth muscle actin, desmin, or FSP-1. Moreover, cells genetically labeled by FSP-1(YFP) expression did not coexpress cholangiocyte markers K19 or E-cadherin. Genetically labeled GFAP(GFP) HSCs did not express epithelial or liver progenitor markers in response to liver injury. Conclusion: EMT of cholangiocytes identified by genetic labeling does not contribute to hepatic fibrosis in mice. Likewise, GFAP(Cre)-labeled HSCs showed no coexpression of epithelial markers, providing no evidence for MET in HSCs in response to fibrogenic liver injury. (Copyright © 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.) |
التعليقات: | Comment in: Gastroenterology. 2010 Sep;139(3):722-5. (PMID: 20682361) |
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معلومات مُعتمدة: | P50 AA011999 United States AA NIAAA NIH HHS; P50 AA011999-11 United States AA NIAAA NIH HHS; 2 P50 AA011999-11 United States AA NIAAA NIH HHS |
المشرفين على المادة: | 0 (Biomarkers) 0 (Calcium-Binding Proteins) 0 (Collagen Type II) 0 (Glial Fibrillary Acidic Protein) 0 (Gt(ROSA)26Sor non-coding RNA, mouse) 0 (Keratin-19) 0 (Luminescent Proteins) 0 (Proteins) 0 (RNA, Untranslated) 0 (S100 Calcium-Binding Protein A4) 0 (S100 Proteins) 0 (S100a4 protein, mouse) CL2T97X0V0 (Carbon Tetrachloride) |
تواريخ الأحداث: | Date Created: 20100616 Date Completed: 20100920 Latest Revision: 20220318 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC2930026 |
DOI: | 10.1053/j.gastro.2010.05.005 |
PMID: | 20546735 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1528-0012 |
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DOI: | 10.1053/j.gastro.2010.05.005 |