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Klin Padiatr 2015; 227(01): 15-22
DOI: 10.1055/s-0034-1389906
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Modifications in Integrin Expression and Extracellular Matrix Composition in Children with Biliary Atresia

Veränderungen der Integrin-Expression und Zusammensetzung der extrazellulären Matrix bei Kindern mit Gallangangsatresie
T. Whitby
1   Paediatric Gastroenterology, Hepatology and Nutrition, Alder Hey Children’s NHS Foundation Trust, Liverpool, United Kingdom
,
D. Schroeder
2   Paediatric Gastroenterology, Hepatology and Liver Transplant, University Hospital Essen, Germany
,
H. S. Kim
2   Paediatric Gastroenterology, Hepatology and Liver Transplant, University Hospital Essen, Germany
,
C. Petersen
3   Paediatric Surgery, Medical School Hannover, Germany
,
O. Dirsch
4   Institute of Pathology, University Hospital Jena, Germany
,
U. Baumann
5   Liver Unit, Children’s Hospital and University Hospital Birmingham, United Kingdom
6   Paediatric Gastroenterology, Medical School Hannover, Germany
,
M.K. H. Auth
1   Paediatric Gastroenterology, Hepatology and Nutrition, Alder Hey Children’s NHS Foundation Trust, Liverpool, United Kingdom
2   Paediatric Gastroenterology, Hepatology and Liver Transplant, University Hospital Essen, Germany
› Institutsangaben
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Publikationsverlauf

Publikationsdatum:
07. Januar 2015 (online)

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Abstract

Background: The aetiology of biliary atresia (BA) is still unresolved. The study’s aim was to investigate the distribution of extracellular matrix proteins and cellular adhesion molecules in children with BA compared to other cholestatic liver disease (CLD) and normal liver architecture (NLA).

Patients: Liver biopsies were obtained from children with BA (n=13), CLD (n=6) and NLA (n=8).

Method: We systematically analysed ultra thin frozen sections from the liver hilum stained with 25 monoclonal antibodies for cellular characterisation, extracellular matrix proteins and adhesion molecules.

Results: 2 changes were specifically found in BA: laminin beta1 was reduced in children with BA vs. NLA and CLD. Conversely, integrin alpha 3 was increased in BA vs. NLA and CLD (p<0.05). Furthermore, we detected changes in a similar pattern for both BA and CLD vs. NLA: in BA and CLD perlecan was increased. On the contrary, integrin beta1 and entactin were decreased vs. NLA (p<0.05).

Discussion: Extracellular matrix proteins and adhesion molecules mediate cellular polarity and integrity, development of tubular structures, and proliferation. Therefore, our findings can be important for the understanding of the genesis of BA.

Conclusion: The composition of extracellular matrix proteins and adhesion molecules in children with BA differs from NLA and other CLD in distribution of laminin beta1 and integrin alpha 3, which may have implications for genetic, immunologic and environmental associations in BA.

Zusammenfassung

Hintergrund: Die Ätiologie der Gallangangsatresie (BA) ist immer noch ungeklärt. Ziel dieser Arbeit war es, die Verteilung der extrazellulären Matrixproteine und zellulären Adhäsionsmoleküle von Kindern mit BA mit anderen Formen cholestatischer Lebererkrankungen (CLD) oder mit normaler Zellarchitektur (NLA) zu vergleichen.

Patienten: Leberbiopsien wurden von 13 Kindern mit BA, 6 Kindern mit CLD und 8 Kindern mit NLA entnommen.

Methoden: Wir untersuchten systematisch an gefriergetrockneten Ultradünnschnitten die Verteilung der extrazellulären Matrixproteine und spezifischen Adhäsionsmoleküle des Gallengangsepithels im Bereich der Leberpforte. Durch semiquantitative Analyse der immunphänotypisch charakterisierten Gallenwegsstrukturen wurden statistisch signifikante Unterschiede der strukturellen Expressionsmuster von 25 spezifischen, monoklonalen Antikörpern ermittelt.

Ergebnisse: In unseren Untersuchungen zeigten sich 2 spezifische Veränderungen für BA: im Vergleich zu Kindern mit NLA oder CLD war Laminin beta1 bei BA reduziert. Im Gegensatz dazu war Integrin alpha3 bei BA erhöht (p<0,05). Darüberhinaus fanden sich korrespondierende Veränderungen, die sowohl BA als auch CLD gegenüber NLA betrafen: eine verstärkte Proteinexpression von Perlecan wurde für BA und CLD nachwiesen. Demgegenüber zeigte sich eine Reduktion von Integrin beta1 und Entaktin im Vergleich zu NLA (p<0,05).

Diskussion: Extrazelluläre Matrixproteine und Adhäsionsmoleküle beeinflussen die zelluläre Polarität und Integrität, Entwicklung von tubulären Strukturen und Proliferation, daher können unsere Ergebnisse bedeutsam für die Genese der BA sein.

Schlussfolgerung: Die Zusammensetzung der extrazellulären Matrixproteine und Adhäsionsmoleküle bei Kindern mit BA unterscheidet sich von denen mit NLA. Dies könnte bedeutsam für genetische, immunologische und Umweltfaktoren der BA sein.

Key words

biliary atresia - biliary epithelial cells - extracellular matrix - integrins - laminin

Schlüsselwörter

Gallengangsatresie - Gallengangs-Epithelzellen - extrazelluläre Matrix - Integrine - Laminin

Supplementary Material

 

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