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Inhibition of PKHD1 may cause S‐phase entry via mTOR signaling pathway
Author(s) -
Zheng Rong,
Wang Li,
Fan Junming,
Zhou Qin
Publication year - 2009
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1016/j.cellbi.2009.06.012
Subject(s) - pi3k/akt/mtor pathway , microbiology and biotechnology , chemistry , signal transduction , biology
Abstract Autosomal recessive polycystic kidney disease (ARPKD) is an important genetic disorder in pediatric nephrological practice. Mutation of the polycystic kidney and hepatic disease gene 1 ( PKHD1 ) was identified as the cause of ARPKD. Rapamycin is a highly specific inhibitor of mammalian target of rapamycin (mTOR). Rapamycin exerts its biological activity by inhibiting the serine–threonine kinase mTOR, which regulates important cellular processes such as control of cell cycle, cell size, translation initiation and transcription. The ability of rapamycin to cause G1‐cell cycle arrest, reduced cell growth and a reduced rate of proliferation has led to efforts to develop rapamycin and related mTOR inhibitors as anti‐cystogenesis agents. Therefore, we investigated the relationship between the decreased FPC and the protein levels of mTOR and the inhibitory effects of rapamycin on the expression of mTOR, Hypoxia‐inducible factor‐1 alpha (HIF‐1α) and vascular endothelial growth factor (VEGF) in the human 293T cell line. These observations should provide an important platform for determining FPC function and the pathogenesis of ARPKD, with the targeting of mTOR signaling being exploitable as a novel therapy.