Increased MMP‐7 expression in biliary epithelium and serum underpins native liver fibrosis after successful portoenterostomy in biliary atresia

The molecular mechanisms underlying progressive liver fibrosis following surgical treatment of biliary atresia (BA) remain unclear. Our aim was to address hepatic gene and protein expression and serum levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) after successful por...

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Bibliographic Details
Published in:The journal of pathology. Clinical research 2016-07, Vol.2 (3), p.187-198
Main Authors: Kerola, Anna, Lampela, Hanna, Lohi, Jouko, Heikkilä, Päivi, Mutanen, Annika, Hagström, Jaana, Tervahartiala, Taina, Sorsa, Timo, Haglund, Caj, Jalanko, Hannu, Pakarinen, Mikko P.
Format: Article
Language:English
Subjects:
Administrative support
Bile
Bile ducts
Biliary atresia
Biochemical markers
Blood platelets
Cholestasis
Cytokeratin
cytokeratin‐7
ductal proliferation
Epithelium
Fibrosis
Gallbladder diseases
Gene expression
Hepatocytes
hepatocyte‐to‐cholangiocyte metaplasia
Hyperactivity
Immune clearance
Immunohistochemistry
Intestine
Liver diseases
Matrix metalloproteinase
Medicin och hälsovetenskap
Molecular modelling
Original
Patients
portal fibrosis
Serum levels
serum marker of fibrosis
Studies
Therapeutic applications
tissue inhibitor of matrix metalloproteinases
Tissue inhibitor of metalloproteinases
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Summary:The molecular mechanisms underlying progressive liver fibrosis following surgical treatment of biliary atresia (BA) remain unclear. Our aim was to address hepatic gene and protein expression and serum levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) after successful portoenterostomy (PE), and relate them to histological signs of liver injury, clinical follow‐up data and biochemical markers of hepatic function. LIver biopsies and serum samples were obtained from 25 children after successful PE at median age of 3.3 years. Serum MMP concentrations were determined by enzyme‐linked immune sorbent assay. Hepatic gene expression of MMPs and TIMPs was analyzed using real‐time reverse‐transcription PCR. Liver expression of MMP‐7 and cytokeratin‐7 was studied using immunohistochemistry. Despite effective clearance of biochemical and histological cholestasis following PE, BA patients showed increased hepatic gene expression of MMP‐7 (29‐fold, p 
ISSN:2056-4538
2056-4538
DOI:10.1002/cjp2.50