2007/08/23 by Thomas Weimbs · 2 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Acute kidney injury #Autosomal dominant polycystic kidney disease #Biology #Cancer research #Cell biology #Cilium #Endocrinology #Genetic and Kidney Cyst Diseases #Hedgehog Signaling Pathway Studies #Internal medicine #Kidney #Mechanotransduction #Medicine #PI3K/AKT/mTOR pathway #PKD1 #Polycystic kidney disease #Renal and related cancers #Signal transduction
paper · doi:10.1152/ajprenal.00275.2007
openalex publication_date 2007/08/23 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/15
The root cause for most cases of autosomal-dominant polycystic kidney disease (ADPKD) is mutations in the polycystin-1 (PC1) gene. While PC1 has been implicated in a perplexing variety of protein interactions and signaling pathways, what its normal function is and why its disruption leads to the proliferation of renal epithelial cells are unknown. Recent results suggest that PC1 is involved in mechanotransduction by primary cilia measuring the degree of luminal fluid flow. PC1 has also recently been shown to regulate the mTOR and signal transducers and activators of transcription (STAT) 6 pathways. These two pathways are normally dormant in the healthy kidney but are activated in response to injury and appear to drive a proliferative repair response. This review develops the idea that a critical function of PC1 and primary cilia in the adult kidney may be to sense renal injury by detecting changes in luminal fluid flow and to trigger proliferation. Constitutive activation of these pathways in ADPKD would lead to the futile attempt to repair a nonexisting injury, resulting in cyst growth. The existence of many known cellular and molecular similarities between renal repair and ADPKD supports this model.