Kentucky Community & Technical College System
A Theoretical Mechanism for Caffeine-Induced Cystogenesis in Polycystic Kidney Disease
Faculty Advisor/ Mentor
Timothy Dick; Kathy Hoffman
Abstract
Polycystic kidney disease (PKD) occurs when one of two genes, the PKD 1 gene on Chromosome 16 or the PKD 2 gene on Chromosome 4, is mutated, leading to the development of cysts in affected individuals. The protein products, polycystin 1 and polycystin 2, activate the WNT pathway, a signaling cascade that can control cell proliferation. These proteins also activate cAMP, a second messenger in the cell. Since caffeine increases cAMP levels, use of this substance may lead to the phosphorylation of a specific WNT pathway kinase called ERK. The phosphorylation of ERK ultimately leads to the activation of specific transcription factors which control genes responsible for the regulation of cell proliferation. An individual with PKD already has a malfunctioning WNT cascade; thus caffeine may hasten cystogenesis. This study constructs a theoretical mechanism for the role of caffeine in cystogenesis. The mechanism will be tested in future research by exposing Zebra fish (Danio rerio) to an aquatic environment containing caffeine. Since their embryos are clear and kidney development consists of a single tubular structure, a cyst is easily detected.
A Theoretical Mechanism for Caffeine-Induced Cystogenesis in Polycystic Kidney Disease
Polycystic kidney disease (PKD) occurs when one of two genes, the PKD 1 gene on Chromosome 16 or the PKD 2 gene on Chromosome 4, is mutated, leading to the development of cysts in affected individuals. The protein products, polycystin 1 and polycystin 2, activate the WNT pathway, a signaling cascade that can control cell proliferation. These proteins also activate cAMP, a second messenger in the cell. Since caffeine increases cAMP levels, use of this substance may lead to the phosphorylation of a specific WNT pathway kinase called ERK. The phosphorylation of ERK ultimately leads to the activation of specific transcription factors which control genes responsible for the regulation of cell proliferation. An individual with PKD already has a malfunctioning WNT cascade; thus caffeine may hasten cystogenesis. This study constructs a theoretical mechanism for the role of caffeine in cystogenesis. The mechanism will be tested in future research by exposing Zebra fish (Danio rerio) to an aquatic environment containing caffeine. Since their embryos are clear and kidney development consists of a single tubular structure, a cyst is easily detected.