Oxalate regulates crystal-cell adhesion and macrophage metabolism via JPT2/PI3K/AKT signaling to promote the progression of kidney stones  

作　　者：Qianlin Song Chao Song Xin Chen Yunhe Xiong Ziqi He Xiaozhe Su Jiawei Zhou Hu Ke Caitao Dong Wenbiao Liao Sixing Yang 

机构地区：[1]Department of Urology,Renmin Hospital of Wuhan University,Wuhan,430060,China [2]Department of Obstetrics and Gynecology,Renmin Hospital of Wuhan University,Wuhan,430060,China

出　　处：《Journal of Pharmaceutical Analysis》2024年第6期851-862,共12页药物分析学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant Nos.:82070723,82270797);Nature Science Foundation of Hubei Province,China(Grant No.:2022CFC020).

摘　　要：Oxalate is an organic dicarboxylic acid that is a common component of plant foods.The kidneys are essential organs for oxalate excretion,but excessive oxalates may induce kidney stones.Jupiter microtubule associated homolog 2(JPT2)is a critical molecule in Ca^(2+)mobilization,and its intrinsic mechanism in oxalate exposure and kidney stones remains unclear.This study aimed to reveal the mechanism of JPT2 in oxalate exposure and kidney stones.Genetic approaches were used to control JPT2 expression in cells and mice,and the JPT2 mechanism of action was analyzed using transcriptomics and untargeted metabolomics.The results showed that oxalate exposure triggered the upregulation of JPT2,which is involved in nicotinic acid adenine dinucleotide phosphate(NAADP)-mediated Ca^(2+)mobilization.Transcriptomic analysis revealed that cell adhesion and macrophage inflammatory polarization were inhibited by JPT2 knockdown,and these were dominated by phosphatidylinositol 3-kinase(PI3K)/AKT signaling,respectively.Untargeted metabolomics indicated that JPT2 knockdown inhibited the production of succinic acid semialdehyde(SSA)in macrophages.Furthermore,JPT2 deficiency in mice inhibited kidney stones mineralization.In conclusion,this study demonstrates that oxalate exposure facilitates kidney stones by promoting crystal-cell adhesion,and modulating macrophage metabolism and inflammatory polarization via JPT2/PI3K/AKT signaling.

关 键 词：OXALATE Kidney stones JPT2 Crystal-cell adhesion IMMUNOREGULATION 

分 类 号：R285.5[医药卫生—中药学]