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

Show full item record



Permalink

http://hdl.handle.net/10138/175025

Citation

Kerola , A , Lampela , H , Lohi , J , Heikkilä , P , Mutanen , A , Hagström , J , Tervahartiala , T , Sorsa , T , Haglund , C , Jalanko , H & Pakarinen , M P 2016 , ' Increased MMP-7 expression in biliary epithelium and serum underpins native liver fibrosis after successful portoenterostomy in biliary atresia ' , The Journal of Pathology. Clinical Research , vol. 2 , no. 3 , pp. 187-198 . https://doi.org/10.1002/cjp2.50

Title: Increased MMP-7 expression in biliary epithelium and serum underpins native liver fibrosis after successful portoenterostomy in biliary atresia
Author: Kerola, Anna; Lampela, Hanna; Lohi, Jouko; Heikkilä, Päivi; Mutanen, Annika; Hagström, Jaana; Tervahartiala, Taina; Sorsa, Timo; Haglund, Caj; Jalanko, Hannu; Pakarinen, Mikko Petteri
Contributor: University of Helsinki, Clinicum
University of Helsinki, Department of Pathology
University of Helsinki, Department of Pathology
University of Helsinki, Clinicum
University of Helsinki, Clinicum
University of Helsinki, Clinicum
University of Helsinki, Clinicum
University of Helsinki, Clinicum
University of Helsinki, Children's Hospital
University of Helsinki, Lastenkirurgian yksikkö
Date: 2016-05-12
Language: eng
Number of pages: 12
Belongs to series: The Journal of Pathology. Clinical Research
ISSN: 2056-4538
URI: http://hdl.handle.net/10138/175025
Abstract: 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 <0.001), MMP-2 (3.1-fold, p <0.001), MMP-14 (1.7-fold, p 50.007), and TIMP-1 (1.8-fold, p <0.001), when compared to controls. Similar to a biliary epithelial marker cytokeratin-7, expression of MMP-7 localized in biliary epithelium of bile ducts and ductal proliferations and periportal hepatocytes and was increased (p <0.001) in relation to controls. BA patients had 6-fold higher serum levels of MMP-7 (p <0.001), which correlated positively with hepatic MMP-7 gene (r 50.548, p 50.007) and protein (r 50.532, p 50.007) expression. Patients showed a positive correlation between biliary MMP-7 expression and Metavir fibrosis stage (r 50.605, p 50.001) and portal fibrosis grade (r 50.606, p 50.001). Neither similarly increased MMP-7 expression nor correlation with liver fibrosis was observed in patients with intestinal failure-associated liver disease and comparable Metavir stage. In conclusion, our findings support an unique role of altered hepatic expression of MMP-7 in the progression of liver fibrosis after successful PE and introduce a potential therapeutic target to pharmacologically extend native liver survival by inhibiting MMP-7 hyperactivity. Serum MMP-7 may be a valuable postoperative prognostic tool in BA.
Subject: 3126 Surgery, anesthesiology, intensive care, radiology
Rights:


Files in this item

Total number of downloads: Loading...

Files Size Format View
cjp250.pdf 608.3Kb PDF View/Open

This item appears in the following Collection(s)

Show full item record