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Integrin Beta-8, But Not Beta-5 or -6, Protein Expression is Increased in Livers of Children With Biliary Atresia.
MedLine Citation:
PMID:  25079481     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
INTRODUCTION:: Our previous work demonstrated altered mRNA expression of integrin beta 5 and 8, using an in silico analysis of publically available data from patients with BA, however we were unable to demonstrate statistically significant differences in protein expression due to sample size. In this experiment, we repeated the analysis of liver fibrosis and protein expression of the integrins in a larger cohort of patients with BA and compared them to patients undergoing liver biopsy for other diagnoses, with the hypothesis that one or more of the integrins would be differentially expressed.
METHODS:: Liver specimens were obtained at two collaborating institutions. Samples from infants with BA (n = 23) were compared to those who underwent liver biopsy for neonatal hepatitis (n = 9). All specimens were analyzed by two pathologists, (CR and RA), who were blinded to the diagnoses. Standard Ishak scoring was performed to evaluate fibrosis and inflammation, and IHC positivity was graded from 0 to 4. Comparisons between the IHC positivity and Ishak scoring for the BA and control groups were performed using Student's t-test with P < 0.01 considered significant due to the multiple comparisons. Inter-observer variability was assessed by Intra-class Correlation.
RESULTS:: Pooled analysis from specimens from patients with BA showed significantly more fibrosis than controls based on Ishak scores (3.21 ± 1.82 vs 1.17 ± 1.00, P < 0.005) (Table 2). IHC evaluation showed increased integrin ανβ8 protein expression when compared with controls (2.67 ± 0.81 vs 1.72 ± 0.62, P < 0.005). However, there were no significant differences in integrin ανβ5 (1.93 ± 0.84 vs 1.50 ± 0.90, P = 0.23) or integrin ανβ6 expression (0.85 ± 1.20 vs 0.94 ± 0.85, P = 0.82). These data were confirmed on individual analysis. Inter-observer agreement was fair for integrin ανβ5 (ICC = 0.52), good for integrin ανβ6 (ICC = 0.72), and excellent for integrin ανβ8 (ICC = 0.79) and fibrosis (ICC = 0.89).
CONCLUSION:: Our data show that integrin ανβ8, but not integrin ανβ5 or integrin ανβ6, protein expression is increased in liver specimens of patients with BA. These data support the mounting evidence that TGF-β activation is responsible for the fibrosis found in BA. Anti- integrin ανβ8 or more global integrin blocking strategies may be potential therapeutic options in BA but further work is clearly needed.
Authors:
Tatiana Iordanskaia; Emily Koeck; Christopher Rossi; Parvathi Mohan; Kathleen Schwarz; Robert Anders; Evan P Nadler
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-7-30
Journal Detail:
Title:  Journal of pediatric gastroenterology and nutrition     Volume:  -     ISSN:  1536-4801     ISO Abbreviation:  J. Pediatr. Gastroenterol. Nutr.     Publication Date:  2014 Jul 
Date Detail:
Created Date:  2014-7-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8211545     Medline TA:  J Pediatr Gastroenterol Nutr     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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