title: Distribution of alpha-integrin subunits in fetal polycystic kidney diseases.
abstract: An alteration in cell/matrix interactions is one of the suggested mechanisms leading to cyst formation in polycystic kidney diseases. Most of these interactions are mediated by beta 1-integrins, a subfamily of integrin receptors, formed by the association of the beta 1-chain with different alpha-subunits. To date, no study on alpha-integrin subunit distribution during the early stages of cyst development has been reported. Using immunofluorescence, we analyzed the distribution of alpha-integrin subunits (alpha 1, alpha 2, alpha 3, alpha 5, and alpha 6) and basement membrane proteins in kidneys of fetuses with autosomal dominant (ADPKD) or autosomal recessive polycystic kidney disease (ARPKD). The distribution was compared with that observed in normal fetal and post-natal kidneys, and in fetal cystic dysplasia and Meckel syndrome. Marked increase in alpha 1-integrin staining was observed in normal and cystic collecting duct cells of both polycystic diseases (PKD), compared with normal and cystic controls. The distribution of integrin subunits alpha 2, alpha 3, and alpha 6 was irregular in cyst epithelial cells of PKD and cystic controls. The increased expression of the alpha 1-subunit specifically observed in PKD collecting duct cells may be an early consequence of the genetic defect in ARPKD. In ADPKD it parallels the reported expression of polycystin, the protein product of PKD1. The irregular expression of alpha 2, alpha 3, and alpha 6 integrin subunits observed in all types of cysts suggests that cell/matrix interactions are altered early and may participate in the development of cysts, perhaps by contributing to the deregulation of cell survival in cystic diseases.
authors.affiliation: Inserm U. 423, Hôpital Necker-Enfants Malades, Université René Descartes, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Daïkha-Dahmane
authors.forename: F
authors.initials: F
authors.lastname: Narcy
authors.forename: M
authors.initials: M
authors.lastname: Dommergues
authors.forename: M
authors.initials: M
authors.lastname: Lacoste
authors.forename: A
authors.initials: A
authors.lastname: Beziau
authors.forename: M C
authors.initials: MC
authors.lastname: Gubler
mesh_terms: D000911:Antibodies, Monoclonal; D001485:Basement Membrane / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007231:Infant, Newborn; D016023:Integrins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D007690:Polycystic Kidney Diseases / Q000378:metabolism*; D016891:Polycystic Kidney, Autosomal Dominant / Q000378:metabolism / Q000473:pathology; D017044:Polycystic Kidney, Autosomal Recessive / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy
chemical_list: D000911:Antibodies, Monoclonal; D016023:Integrins; D008565:Membrane Proteins