دورية أكاديمية
أعرض في EDS

Genetic labeling does not detect epithelial-to-mesenchymal transition of cholangiocytes in liver fibrosis in mice.

التفاصيل البيبلوغرافية
العنوان: Genetic labeling does not detect epithelial-to-mesenchymal transition of cholangiocytes in liver fibrosis in mice.
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
الوصف
تدمد:1528-0012
DOI:10.1053/j.gastro.2010.05.005