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Trps1 regulates biliary epithelial-mesenchymal transition and has roles during biliary fibrosis in liver grafts: a preliminary study
- Source :
- PLoS ONE, Vol 10, Iss 4, p e0123233 (2015), PLoS ONE
- Publication Year :
- 2015
- Publisher :
- Public Library of Science (PLoS), 2015.
-
Abstract
- Objective To investigate the role(s) of Trps1 in non-anastomotic biliary stricture (NABS) following liver transplantation. Methods Immunohistochemical and histological techniques were used to detect Trps1, E-cadherin, CK19, vimentin, α-SMA, and collagen deposition. Human intrahepatic biliary epithelial cells (HIBECs) were infected with a Trps1 adenovirus, or transfected with Trps1 short-interfering RNAs (siRNAs). Reverse transcription polymerase chain reaction (RT-PCR) assays and western blotting were used to determine expression levels of epithelial and mesenchymal markers, and Trps1 in HIBECs. Results Expression of Trps1 and epithelial markers was down-regulated or absent in NABS liver samples. Mesenchymal markers were seen in biliary epithelial cells (BECs), with collagen deposited around the bile duct. Trps1 expression positively correlated with epithelial markers. Expression of epithelial marker mRNAs and proteins in HIBECs decreased with prolonged cold preservation (CP), while mesenchymal marker expression increased. A 12-h CP period led to increased Trps1 mRNA and protein levels. Expression of E-cadherin was increased in HIBECs following Trps1 adenovirus infection and CP/reperfusion injury (CPRI), with vimentin expression levels reduced and CPRI-mediated epithelial-mesenchymal transition (EMT) inhibited. Transfection of HIBECs with Trps1 siRNAs in conjunction with CPRI revealed that E-cadherin expression was decreased, vimentin expression was increased, and CPRI-mediated EMT was promoted. Conclusion Trps1 is involved in NABS pathogenesis following liver transplantation and negatively correlates with BEC EMT and biliary fibrosis in liver grafts. Trps1 demonstrates antagonistic effects that could reverse EMT.
- Subjects :
- Adult
Male
Pathology
medicine.medical_specialty
Epithelial-Mesenchymal Transition
medicine.medical_treatment
lcsh:Medicine
Vimentin
Liver transplantation
Biology
Fibrosis
medicine
Humans
Epithelial–mesenchymal transition
Adenovirus infection
lcsh:Science
Multidisciplinary
Liver Diseases
Mesenchymal stem cell
lcsh:R
Middle Aged
Cadherins
medicine.disease
Liver Transplantation
DNA-Binding Proteins
Repressor Proteins
Blot
Reverse transcription polymerase chain reaction
Cancer research
biology.protein
Female
lcsh:Q
Bile Ducts
Research Article
Transcription Factors
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 10
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....4186f46358e2898594c44dc8ad5c1441