| First Author | Lin X | Year | 2014 |
| Journal | J Am Soc Nephrol | Volume | 25 |
| Issue | 4 | Pages | 687-92 |
| PubMed ID | 24262794 | Mgi Jnum | J:207595 |
| Mgi Id | MGI:5559174 | Doi | 10.1681/ASN.2013070798 |
| Citation | Lin X, et al. (2014) Feasibility of repairing glomerular basement membrane defects in alport syndrome. J Am Soc Nephrol 25(4):687-92 |
| abstractText | Alport syndrome is a hereditary glomerular disease that leads to kidney failure. It is caused by mutations affecting one of three chains of the collagen alpha3alpha4alpha5(IV) heterotrimer, which forms the major collagen IV network of the glomerular basement membrane (GBM). In the absence of the alpha3alpha4alpha5(IV) network, the alpha1alpha1alpha2(IV) network substitutes, but it is insufficient to maintain normal kidney function. Inhibition of angiotensin-converting enzyme slows progression to kidney failure in patients with Alport syndrome but is not a cure. Restoration of the normal collagen alpha3alpha4alpha5(IV) network in the GBM, by either cell- or gene-based therapy, is an attractive and logical approach toward a cure, but whether or not the abnormal GBM can be repaired once it has formed and is functioning is unknown. Using a mouse model of Alport syndrome and an inducible transgene system, we found that secretion of alpha3alpha4alpha5(IV) heterotrimers by podocytes into a preformed, abnormal, filtering Alport GBM is effective at restoring the missing collagen IV network, slowing kidney disease progression, and extending life span. This proof-of-principle study demonstrates the plasticity of the mature GBM and validates the pursuit of therapeutic approaches aimed at normalizing the GBM to prolong kidney function. |
