| Autor: |
Yong Wu, Jen X. Xu, El-Jouni, Wassim, Tzongshi Lu, Suyan Li, Qingyi Wang, Mei Tran, Wanfeng Yu, Maoqing Wu, Barrera, Ivan E., Bonventre, Joseph V., Jing Zhou, Denker, Bradley M., Tianqing Kong |
| Předmět: |
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| Zdroj: |
Journal of Cell Science; 10/1/2016, Vol. 129 Issue 19, p3675-3684, 10p |
| Abstrakt: |
Mutation of PKD1, encoding the protein polycystin-1 (PC1), is themain cause of autosomal dominant polycystic kidney disease (ADPKD). The signaling pathways downstream of PC1 in ADPKD are still not fully understood. Here, we provide genetic evidence for the necessity of Gα12 (encoded by Gna12, hereafter Gα12) for renal cystogenesis induced by Pkd1 knockout. There was no phenotype in mice with deletion of Gα12 (Gα12-/-). Polyinosine-polycytosine (pI:pC)-induced deletion of Pkd1 (Mx1Cre+Pkd1f/fGα12+/+) in 1-week-old mice resulted in multiple kidney cysts by 9 weeks, but the mice with double knockout of Pkd1 and Gα12 (Mx1Cre+Pkd1f/fGα12-/-) had no structural and functional abnormalities in the kidneys. These mice could survive more than one year without kidney abnormalities except multiple hepatic cysts in some mice, which indicates that the effect of Gα12 on cystogenesis is kidney specific. Furthermore, Pkd1 knockout promoted Gα12 activation, which subsequently decreased cell--matrix and cell--cell adhesion by affecting the function of focal adhesion and E-cadherin, respectively. Our results demonstrate that Gα12 is required for the development of kidney cysts induced by Pkd1 mutation in mouse ADPKD. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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