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) : Gusella, Gabriele L


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a562319.pdf


Report Date : Apr 2012


Pagination or Media Count : 8


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 Pkd1/Itgb1 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.


Descriptors :   *KIDNEY DISEASES , ABLATION , CYSTS , FIBROSIS , IN VIVO ANALYSIS , KIDNEYS , SYNCHRONISM


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE