Accession Number:

ADA562319

Title:

Role of Integrin-Beta1 in Polycystic Kidney Disease

Descriptive Note:

Annual rept. 1 Apr 2011-31 Mar 2012

Corporate Author:

MOUNT SINAI SCHOOL OF MEDICINE NEW YORK

Personal Author(s):

Report Date:

2012-04-01

Pagination or Media Count:

8.0

Abstract:

Increased fibrosis and integrins expression are elevated in in APDKD. The scope of the study is to assess whether integrin beta1 Int 1 plays a role in the ADPKD. The past funding period has focused primarily on the in vivo study of the role of in the cystogenic process. We have generated conditional double knockout mice where both Itgb1 and Pkd1 genes can be simultaneously deleted. As previously described, the single conditional Pkd1 knockout develops an overt cystic phenotype by 4 weeks, whereas the conditional deletion of Itgb1 had no observable effects. Interestingly, the simultaneous ablation of Itgb1 in compound Pkd1Itgb1 knockout mice significantly prevented renal cystic development. Correspondingly, while the renal function of the Pkd1 knockout mice was significantly declined in time, it remained unaffected in the double knockout mice for all the time points so far tested. Although the studies are still ongoing, these findings support the initial hypothesis that Int 1 is an essential mediator in ADPKD cystogenesis. These results indicate that the signaling pathway controlled by Int 1 could be successfully targeted to prevent or slow down the cystic development.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE