gsk2256098 and Polycystic-Kidney--Autosomal-Dominant

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by numerous cysts originating from renal tubules and is associated with significant tubular epithelial cell proliferation. Focal adhesion kinase (FAK) promotes tumor growth by regulating multiple proliferative pathways.. We established the forskolin (FSK)-induced three-dimensional (3D) Madin-Darby Canine Kidney cystogenesis model and 8-bromoadenosine-3`,5`-cyclic monophosphate-stimulated cyst formation in. FAK activity was significantly elevated in OX-161 cells and in two ADPKD mouse models. Inhibiting FAK activity reduced cell proliferation in OX-161 cells and prevented cyst growth in. Our study demonstrates the critical involvement of FAK in renal cyst development, suggests that FAK is a potential therapeutic target in treating patients with ADPKD, and highlights the role of FAK in cAMP-PKA-regulated proliferation.

Topics: Aminopyridines; Animals; Benzamides; Cell Culture Techniques; Cell Proliferation; Disease Models, Animal; Dogs; Epithelial Cells; Focal Adhesion Protein-Tyrosine Kinases; Humans; Hydroxamic Acids; Mice; Mice, Inbred C57BL; Polycystic Kidney, Autosomal Dominant; Pyrazines; Signal Transduction; Sulfonamides