title: Decreased expression of vitamin K epoxide reductase complex subunit 1 in kidney of patients with calcium oxalate urolithiasis.
abstract: Urinary prothrombin fragment 1 (UPTF1) is a potent inhibitor of urinary stone formation. UPTF1 exerts such inhibitory effect by effective γ-carboxylation in which vitamin K epoxide reductase complex subunit 1 (VKORC1), the rate-limiting enzyme, is involved. This study examined the correlation between VKORC1 expression and calcium oxalate urolithiasis. The renal cortex samples were obtained from patients undergoing nephrectomy and then divided into 3 groups: urolithiasis group, control group A [hydronephrosis-without-stone (HWS) group], control group B (normal control group). The localization and expression of VKORC1 in renal tissues were determined by using immunohistochemistry, immunofluorescence microscopy, Western blotting and SYBR Green I real-time reverse-transcription PCR. The rapid amplification of cDNA ends (RACE) were conducted to obtain the 3'- and 5'-untranslated region (UTR) of VKORC1. The results showed that VKORC1 was located in the cytoplasm of renal tubular epithelial cells. The expression of VKORC1 in the urolithiasis group was significantly lower than that in the other two control groups (P<0.05). Moreover, the 3'- and 5'-UTR sequence of the VKORC1 gene was successfully cloned. No insertion or deletion was found in the 3'- and 5'-UTR. However, a 171-bp new base sequence was discovered in the upstream of 5'-UTR end in the urolithiasis group. It was concluded that the decreased expression of VKORC1 may contribute to the development of calcium oxalate urolithiasis in the kidney.
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. twang@tjh.tjmu.edu.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. jhliu@tjh.tjmu.edu.cn.
authors.forename: Jihong
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Shaogang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
authors.forename: Zhangqun
authors.initials: Z
authors.lastname: Ye
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001483:Base Sequence; D002129:Calcium Oxalate / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007669:Kidney Calculi / Q000737:chemistry* / Q000201:enzymology* / Q000601:surgery; D007672:Kidney Cortex / Q000201:enzymology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009392:Nephrectomy; D064417:Vitamin K Epoxide Reductases; D055815:Young Adult
chemical_list: D002129:Calcium Oxalate; D006899:Mixed Function Oxygenases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases