|Author||Lian, Xiaoying ♦ Zhao, Jing ♦ Wu, Xiaoyuan ♦ Zhang, Yingjie ♦ Li, Qinggang ♦ Lin, Shupeng ♦ Bai, Xue-Yuan ♦ Chen, Xiangmei|
|Source||United States Department of Energy Office of Scientific and Technical Information|
|Subject Keyword||APPLIED LIFE SCIENCES ♦ AMP ♦ ANIMAL TISSUES ♦ CELL PROLIFERATION ♦ CYSTS ♦ DISEASES ♦ GLUCOSE ♦ GLYCOLYSIS ♦ KIDNEYS ♦ MITOCHONDRIA ♦ OXIDATION ♦ PHOSPHORYLATION ♦ PHOSPHOTRANSFERASES ♦ RODENTS ♦ SWINE|
|Abstract||The pathogenic mechanism of polycystic kidney disease (PKD) is unclear. Abnormal glucose metabolism is maybe involved in hyper-proliferation of renal cyst epithelial cells. Mini-pigs are more similar to humans than rodents and therefore, are an ideal large animal model. In this study, for the first time, we systematically investigated the changes in glucose metabolism and cell proliferation signaling pathways in the kidney tissues of chronic progressive PKD mini-pig models created by knock-outing PKD1gene. The results showed that in the kidneys of PKD mini-pigs, the glycolysis is increased and the expressions of key oxidative phosphorylation enzymes Complexes I and IV significantly decreased. The activities of mitochondrial respiration chain Complexes I and IV significantly decreased; the phosphorylation level of key metabolism-modulating molecule AMP-activated protein kinase (AMPK) significantly decreased; and the mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) signaling pathway are activated obviously. This study showed that in the kidneys of PKD mini-pigs, the level of glycolysis significantly increased, oxidative phosphorylation significantly decreased, and cell proliferation signaling pathways significantly activated, suggesting that metabolic changes in PKD may result in the occurrence and development of PKD through the activation of proliferation signaling pathways. - Highlights: • Mini-pigs are more similar to humans than rodents and are an ideal animal model. • The study was first performed in chronic model created by knock-outing PKD1gene. • We investigated the changes in glucose metabolism and cell proliferation. • The glycolysis was significantly increased in the kidneys of PKD mini-pigs. • The mTOR and ERK signaling pathway are activated obviously in PKD mini-pigs.|
|Learning Resource Type||Article|
|Publisher Place||United States|
|Journal||Biochemical and Biophysical Research Communications|
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