Activator of G Protein Signaling 3 Promotes Epithelial Cell Proliferation in PKD
Year: 2010
Type: article
Abstract: 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 Galpha subunit function and control epithelial cell function in PKD.
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: Institut National de la Santé et de la Recherche Médicale, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke
Awards: G2465027907, G4143479762, ACCESSORY PROTEINS AND G-PROTEIN SIGNALING MECHANISMS, Defining the role of AGS3 in G protein signal processing, Baltimore Polycystic Kidney Disease Research and Clinical Core Center, AGS4 in G-protein Signal Processing, Accessory proteins and G-protein signaling mechanisms, Novel Therapeutic Strategies for PKD, G6551906533
OpenAlex ID: W2108286451