Glomerular pathology in Alport syndrome: a molecular perspective
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- 作者：Dominic Cosgrove (1) cosgrove@boystown.org
- 关键词：Alport syndrome – ; Glomerular basement membrane – ; Podocyte – ; Pathobiology
- 刊名：Pediatric Nephrology
- 出版年：2012
- 出版时间：June 2012
- 年：2012
- 卷：27
- 期：6
- 页码：885-890
- 全文大小：120.3 KB
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- 刊物类别：Medicine
- 刊物主题：Medicine & Public Health
Pediatrics - 出版者：Springer Berlin / Heidelberg
- ISSN：1432-198X
文摘
We have known for some time that mutations in the genes encoding 3 of the 6 type IV collagen chains are the underlying defect responsible for both X-linked (where the COL4A5 gene is involved) and autosomal (where either COL4A3 or COL4A4 genes are involved) Alport syndrome. The result of these mutations is the absence of the sub-epithelial network of all three chains in the glomerular basement membrane (GBM), resulting, at maturity, in a type IV collagen GBM network comprising only α1(IV) and α2(IV) chains. The altered GBM functions adequately in early life. Eventually, there is onset of proteinuria associated with the classic and progressive irregular thickening, thinning, and splitting of the GBM, which culminates in end-stage renal failure. We have learned much about the molecular events associated with disease onset and progression through the study of animal models for Alport syndrome, and have identified some potential therapeutic approaches that may serve to delay the onset or slow the progression of the disease. This review focuses on where we are in our understanding of the disease, where we need to go to understand the molecular triggers that set the process in motion, and what emergent therapeutic approaches show promise for ameliorating disease progression in the clinic.