Although primary vesical calculi is an ancient disease,the mechanism of calculi formation remains unclear.In this study,we established a novel primary vesical calculi model with D,L-choline tartrate in mice.Compared with commonly used melamine and ethylene glycol models,our model was the only approach that induced vesical calculi without causing kidney injury.Previous studies sug-gest that proteins in the daily diet are the main contributors to the prevention of vesical calculi,yet the effect of fat is overlooked.To assay the relationship of dietary fat with the formation of primary vesical calculi,D,L-choline tartrate-treated mice were fed a high-fat,low-fat,or normal-fat diet.Genetic changes in the mouse bladder were detected with transcriptome analysis.A high-fat diet remarkably reduced the morbidity of primary vesical calculi.Higher fatty acid levels in serum and urine were observed in the high-fat diet group,and more intact epithelia in bladder were observed in the same group compared with the normal-and low-fat diet groups,suggesting the protective effect of fatty acids on bladder epithelia to maintain its normal histological structure.Transcriptome analysis revealed that the macrophage differentiation-related gene C-X-C motif chemokine ligand 14(Cxcl14)was upregulated in the bladders of high-fat diet-fed mice compared with those of normal-or low-fat diet-fed mice,which was consistent with histological observations.The expression of CXCL14 significantly increased in the bladder in the high-fat diet group.CXCL14 enhanced the recruitment of macrophages to the crystal nucleus and induced the transformation of M2 macrophages,which led to phagocytosis of budding crystals and prevented accumulation of calculi.In human bladder epithelia(HCV-29)cells,high fatty acid supplemen-tation significantly increased the expression of CXCL14.Dietary fat is essential for the maintenance of physiological functions of the bladder and for the prevention of primary vesical calculi,which provides new ideas for the reduction of morbidity of primary vesical calculi.

Huiling Chen;Kaiqiang Hu;Yaru Liang;Yuqi Gao;Chenye Zeng;Kang Xu;Xiaojin Shi;Liyuan Li;Yuemiao Yin;Yi Qiao;Ying Qiu;Qingfei Liu;Zhao Wang

School of Pharmaceutical Sciences,Tsinghua University,Beijing 100084,China;Urology Department,Peking Union Medical College Hospital,Beijing 100730,China;School of Medicine,Tsinghua University,Beijing 100084,China

药学学报（英文版）

[1]Huiling Chen;Kaiqiang Hu;Yaru Liang;Yuqi Gao;Chenye Zeng;Kang Xu;Xiaojin Shi;Liyuan Li;Yuemiao Yin;Yi Qiao;Ying Qiu;Qingfei Liu;Zhao Wang-.Ample dietary fat reduced the risk of primary vesical calculi by inducing macrophages to engulf budding crystals in mice)[J].药学学报（英文版）,2022(02):747-758

Ample,vesical,engulf,Cxcl14

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