| Loss of cooperative function of transforming growth factor-beta signaling proteins, smad3 with embryonic liver fodrin, a beta-spectrin, in primary biliary cirrhosis. | |
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MedLine Citation:
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PMID: 15566516 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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METHODS/RESULTS: We investigated the role of ELF in primary biliary cirrhosis (PBC), autoimmune hepatitis C, chronic viral hepatitis and in livers from mice deficient in Smad2/Smad3. We generated elf(+/-) mutant mice and analyzed for chronic liver disease and hepatocellular cancer (HCC) from 6 to 12 months. Perturbations in ELF expression were consistently seen only in PBC tissues. ELF expression was similarly aberrant in tissues from Smad2(+/-)/Smad3(+/-) mutant mice. Further studies indicated that ELF mislocalization is correlated with aberrant localization of Smad3 in some PBC tissues. Thirteen of 17 elf(+/-) mutant mice developed steatosis, fibrosis, hepatic dysplasia, with HCC in two mice. CONCLUSIONS: These results suggest that a compromised cytoarchitecture and polarized trafficking of TGF-beta signaling molecules, ELF and Smad3 are involved in the pathogenesis of PBC as well as HCC. |
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Authors:
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Bibhuti Mishra; Yi Tang; Varalakshmi Katuri; Tom Fleury; Anan H Said; Asif Rashid; Wilma Jogunoori; Lopa Mishra |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Liver international : official journal of the International Association for the Study of the Liver Volume: 24 ISSN: 1478-3223 ISO Abbreviation: Liver Int. Publication Date: 2004 Dec |
Date Detail:
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Created Date: 2004-11-29 Completed Date: 2005-03-22 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 101160857 Medline TA: Liver Int Country: England |
Other Details:
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Languages: eng Pagination: 637-45 Citation Subset: IM |
Affiliation:
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GI/Developmental Biology, Medicine, Surgical Sciences, Lombardi Cancer Center, Georgetown University & DVAMC, Washington, DC, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Base Sequence Biopsy, Needle Blotting, Western Carcinoma, Hepatocellular / genetics*, pathology Carrier Proteins / genetics, metabolism* Cohort Studies DNA-Binding Proteins / genetics, metabolism Ephrin-A2 / genetics* Female Humans Immunohistochemistry Liver Cirrhosis / genetics*, pathology Liver Neoplasms / genetics*, pathology Male Mice Mice, Mutant Strains Microfilament Proteins / genetics, metabolism* Molecular Sequence Data Polymerase Chain Reaction Precancerous Conditions / genetics, pathology Signal Transduction Smad2 Protein Smad3 Protein Spectrin / genetics, metabolism* Trans-Activators / genetics, metabolism Transforming Growth Factor beta / genetics, metabolism Tumor Markers, Biological / analysis Tumor Suppressor Proteins / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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1R01 DK56111/DK/NIDDK NIH HHS; 1R01 DK58637/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Carrier Proteins; 0/DNA-Binding Proteins; 0/Ephrin-A2; 0/Microfilament Proteins; 0/SMAD2 protein, human; 0/SMAD3 protein, human; 0/Smad2 Protein; 0/Smad2 protein, mouse; 0/Smad3 Protein; 0/Smad3 protein, mouse; 0/Trans-Activators; 0/Transforming Growth Factor beta; 0/Tumor Markers, Biological; 0/Tumor Suppressor Proteins; 0/fodrin; 12634-43-4/Spectrin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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