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- Title
Laminin-1 reexpression in Alport mouse glomerular basement membranes<sup>1</sup>.
- Authors
Abrahamson, Dale R.; Prettyman, A. Corinne; Robert, Barry; St. John, Patricia L.
- Abstract
Laminin-1 reexpression in Alport mouse glomerular basement membranes. Background. Alport disease is a heritable basement membrane disorder caused by mutations in genes encoding the α3, α4, or α5 chains of type IV collagen, which normally comprise the collagenous network of mature glomerular basement membranes (GBMs). In Alport disease, the α3(IV), α4(IV), α5(IV) collagen network is absent and substituted for by α1(IV), and α2(IV) collagen, which normally is present only in developing, immature GBMs. The disease is marked by progressive GBM thickening and delamination, proteinuria, and renal failure. In addition to collagen IV dysregulation, abnormal GBM laminins also occur and may contribute to the pathogenesis of Alport glomerulopathy. Methods. To investigate laminin dysregulation in a mouse model of Alport disease, we used antibodies specific for laminin-α1 and -β1 chains (to recognize laminin-1), and -α5 chain (to recognize laminin-11), and evaluated their distribution during glomerular development in α3(IV) collagen-deficient mice. Results. Developing glomeruli of infant α3(IV) collagen knockout mice underwent normal down-regulation of laminin-1, but laminin-1 chains were then reexpressed in maturing glomeruli, becoming concentrated in the subepithelial GBM projections typical of Alport disease. Immunoelectron microscopy showed that laminin-1 reexpression took place in both glomerular endothelial cells and podocytes. Conclusions. The absence of a α3(IV), α4(IV), α5(IV) network may stimulate reexpression of laminin-1 by Alport mouse endothelial cells and podocytes. This abnormal GBM, which is more characteristic of immature glomeruli, may promote podocyte foot process effacement and reversion to a less differentiated state.
- Subjects
ALPORT syndrome; KIDNEY glomerulus
- Publication
Kidney International, 2003, Vol 63, Issue 3, p826
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1046/j.1523-1755.2003.00800.x