Comprehensive identification of stone-promoting proteins in the urine of kidney stone formers

被引:0
作者
Hadpech, Sudarat [1 ]
Peerapen, Paleerath [1 ]
Rattananinsruang, Piyaporn [1 ]
Detsangiamsak, Sasinun [1 ]
Phuangkham, Somsakul [1 ]
Chotikawanich, Ekkarin [2 ]
Sritippayawan, Suchai [3 ]
Thongboonkerd, Visith [1 ,4 ]
机构
[1] Mahidol Univ, Siriraj Hosp, Fac Med, Med Prote Unit,Res Dept, Bangkok 10700, Thailand
[2] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Surg,Div Urol, Bangkok 10700, Thailand
[3] Mahidol Univ, Siriraj Hosp, Fac Med, Dept Med,Div Nephrol, Bangkok 10700, Thailand
[4] Mahidol Univ, Siriraj Hosp, Res Dept, Med Prote Unit, 6th Floor,SiMR Bldg,2 Wanglang Rd, Bangkok 10700, Thailand
关键词
Calcium oxalate; Crystals; Induction; Kidney stone; Modulator; Nephrolithiasis; Promotion; Promotor; CALCIUM-OXALATE MONOHYDRATE; RENAL TUBULAR CELLS; BINDING-PROTEINS; APICAL MEMBRANE; CRYSTAL; UROLITHIASIS; DISEASE; BURDEN; GROWTH; PH;
D O I
10.1016/j.ijbiomac.2025.143251
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Urinary proteins have crucial roles in modulating kidney stone formation. While stone-inhibiting urinary proteins are well characterized, stone-promoting urinary proteins are insufficiently explored. This knowledge gap limits our ability to fully comprehend the pathogenic mechanisms underlying nephrolithiasis and hampers the development of targeted therapeutic/preventive interventions. Therefore, we systematically identified stonepromoting proteins from the urine of 30 calcium oxalate (CaOx) nephrolithiatic patients (stone formers). Urinary proteins were fractionated by anion exchange and size-exclusion chromatography. A total of 15 protein fractions (SF1-SF15) were tested for their modulating activities on CaOx crystals by various assays compared with the control. The fractions with net CaOx-promoting activities were then identified by nanoLC-ESI-Qq-TOF MS/MS. From 15 fractions, 9 had net CaOx-promoting activities in all crystal assays. Among 3-99 proteins identified from these fractions, alpha-1acid glycoprotein 2, alpha-1-antitrypsin, apolipoprotein D, CD44 antigen, endosialin, fibrinogen alpha chain, interleukin-18-binding protein, kallikrein-1, retinol-binding protein 4, and titin have been found to increase in the urine of stone formers compared with controls, reinforcing their potential roles as CaOx stone promoters. This study offers the largest collection of CaOx stone-promoting proteins that will shed light on pathogenic mechanisms of nephrolithiasis and may allow further development of new drug targets to treat/prevent nephrolithiasis.
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页数:16
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