| First Author | Sachs N | Year | 2012 |
| Journal | J Clin Invest | Volume | 122 |
| Issue | 1 | Pages | 348-58 |
| PubMed ID | 22201679 | Mgi Jnum | J:184392 |
| Mgi Id | MGI:5320837 | Doi | 10.1172/JCI58878 |
| Citation | Sachs N, et al. (2012) Blood pressure influences end-stage renal disease of Cd151 knockout mice. J Clin Invest 122(1):348-58 |
| abstractText | Podocytes of the kidney adhere tightly to the underlying glomerular basement membrane (GBM) in order to maintain a functional filtration barrier. The clinical importance of podocyte binding to the GBM via an integrin-laminin-actin axis has been illustrated in models with altered function of alpha3beta1 integrin, integrin-linked kinase, laminin-521, and alpha-actinin 4. Here we expanded on the podocyte-GBM binding model by showing that the main podocyte adhesion receptor, integrin alpha3beta1, interacts with the tetraspanin CD151 in situ in humans. Deletion of Cd151 in mouse glomerular epithelial cells led to reduced adhesive strength to laminin by redistributing alpha3beta1 at the cell-matrix interface. Moreover, in vivo podocyte-specific deletion of Cd151 led to glomerular nephropathy. Although global Cd151-null B6 mice were not susceptible to renal disease, as has been shown previously, increasing blood and transcapillary filtration pressure induced nephropathy in these mice. Importantly, blocking the angiotensin-converting enzyme in renal disease-susceptible global Cd151-null FVB mice prolonged their median life span. Together, these results establish CD151 as a crucial modifier of integrin-mediated adhesion of podocytes to the GBM and show that blood pressure is an important factor in the initiation and progression of Cd151 knockout-induced nephropathy. |
