Endothelial Cell-Specific Collagen IV α3 Expression Does not Rescue Alport Syndrome in Col4a3-/- Mice.

Endothelial Cell-Specific Collagen IV α3 Expression Does not Rescue Alport Syndrome in Col4a3-/- Mice. Am J Physiol Renal Physiol. 2019 Feb 06;: Authors: Funk SD, Bayer RH, Miner JH Abstract The glomerular basement membrane (GBM) is a critical component of the kidney's blood filtration barrier. Alport syndrome, a hereditary disease leading to kidney failure, is caused by the loss or dysfunction of the GBM's major type IV collagen (COL4) isoform, α3α4α5. The constituent COL4 achains assemble into heterotrimers in the endoplasmic reticulum prior to secretion into the extracellular space. If any one of the α3, α4, or α5 chains is lost due to mutation of one of the genes, then the entire heterotrimer is lost. Alport patients typically have mutations in the X-linked COL4A5 gene or uncommonly have the autosomal recessive form of the disease due to COL4A3 or COL4A4 mutations. The treatment for Alport syndrome is currently limited to angiotensin converting enzyme inhibition or angiotensin receptor blockers. Experimental approaches in Alport mice demonstrate that induced expression of COL4A3, either widely or specifically in podocytes of Col4a3-/- mice, can abrogate disease progression even after establishment of the abnormal GBM. While targeting podocytes in vivo for gene therapy is a significant challenge, the more accessible glomerular endothelium could be amenable for mutant gene repair. Herein we expressed COL4A3 in Col4a3-/- Alpo...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research