Increased expression of LCN2 formed a positive feedback loop with activation of the ERK pathway in human kidney cells during kidney stone formation

Kidney stones are a common threat to the health of elderly patients with a high incidence of disease. However, the specific molecular mechanism of the formation of kidney stones has not been elucidated. Here, we combined signalling molecules with signalling pathways in a double positive circulation...

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Published inScientific reports Vol. 10; no. 1; p. 21287
Main Authors Hui, Zhang, Jiang, Zhu, Qiao, Du, Bo, Zhao, Qiyuan, Kang, Shaohua, Bian, Wenbing, Yuan, Wei, Liu, Cheng, Luo, Shuangning, Liu, Zhengyi, Li, Yingyi, Li
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 04.12.2020
Nature Publishing Group UK
Subjects
Calculi
Epithelial cells
Epithelial Cells - metabolism
Extracellular signal-regulated kinase
Feedback, Physiological
HEK293 Cells
Humans
Kidney Calculi - etiology
Kidney Calculi - metabolism
Kidney stones
Kidneys
Lipocalin-2 - metabolism
MAP Kinase Signaling System
Metabolic pathways
Nephrolithiasis
Oxalates
Oxalic acid
Signal transduction
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Summary:Kidney stones are a common threat to the health of elderly patients with a high incidence of disease. However, the specific molecular mechanism of the formation of kidney stones has not been elucidated. Here, we combined signalling molecules with signalling pathways in a double positive circulation regulation model. In addition, we found that LCN2 plays a role in promoting kidney stones through regulation of the ERK signalling pathway and expression of other kidney stone-related genes. LCN2 expression was upregulated upon oxalate stimulation. P-ERK1/2 inhibition by U0126 in kidney epithelial cells resulted in decreased expression of LCN2. Furthermore, the upregulation of LCN2 not only depended on the activation of the ERK signalling pathway but also regulated the activation of the ERK signalling pathway. Importantly, upregulation of LCN2 not only caused kidney epithelial cell damage but also promoted the expression of other kidney stone-related genes. Our findings improved the understanding of LCN2 and might lead to the development of new therapeutic and prognostic markers for kidney stones.
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-75670-w