Decreased Expression of Vitamin K Epoxide Reductase Complex Subunit 1 in Kidney of Patients with Calcium Oxalate Urolithiasis / 华中科技大学学报（医学）（英德文版）

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 VKORC 1 in renal tissues were determined by using immunohistochemistry,immunofluorescence microscopy,Western blotting and SYBR Green Ⅰreal-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 VKORC1was located in the cytoplasm of renal tubular epithelial cells.The expression of VKORC 1 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 VKORC 1 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.