Activator of G Protein Signaling 3 Promotes Epithelial Cell Proliferation in PKD

作者：Nadella Rama; Blumer Joe B; Jia Guangfu; Kwon Michelle; Akbulut Talha; Qian Feng; Sedlic Filip; Wakatsuki Tetsuro; Sweeney William E Jr; Wilson Patricia D; Lanier Stephen M; Park Frank^*

来源：Journal of the American Society of Nephrology, 2010, 21(8): 1275-1280.

DOI：10.1681/ASN.2009121224

The activation of heterotrimeric G protein signaling is a key feature in the pathophysiology of polycystic kidney diseases (PKD). In this study, we report abnormal overexpression of activator of G protein signaling 3 (AGS3), a receptor-independent regulator of heterotrimeric G proteins, in rodents and humans with both autosomal recessive and autosomal dominant PKD. Increased AGS3 expression correlated with kidney size, which is an index of severity of cystic kidney disease. AGS3 expression localized exclusively to distal tubular segments in both normal and cystic kidneys. Short hairpin RNA-induced knockdown of endogenous AGS3 protein significantly reduced proliferation of cystic renal epithelial cells by 26 +/- 2% (P < 0.001) compared with vehicle-treated and control short hairpin RNA-expressing epithelial cells. In summary, this study suggests a relationship between aberrantly increased AGS3 expression in renal tubular epithelia affected by PKD and epithelial cell proliferation. AGS3 may play a receptor-independent role to regulate G alpha subunit function and control epithelial cell function in PKD.

• 出版日期2010-8