Identification of TGF-beta-induced Gene Product, betaig-h3 in Ischemic Acute Renal Failure / 대한신장학회지

ABSTRACT

PURPOSE: Acute renal failure remains a potentially devastating clinical problem. This study aimed to examine whether the expression of TGF-beta-induced gene product, betaig-h3, is altered in ischemia- reperfusion (I/R) injury and urinary excretion of betaig-h3 is changed in I/R injury. METHODS: I/R injury was performed by clamping both renal arteries. Daily urine output, serum creatinine and urinary TGF-beta and betaig-h3 were measured after I/R injury. Also, the renal expression of betaig-h3 by western blotting and immunohistochemistry were investigated. In the second step, urinary betaig-h3 was measured at 4, 10, 16, and 24 hours after I/R injury to investigate whether it could be used as an early and sensitive marker for detecting I/R injury. RESULTS: Urinary betaig-h3 was significantly elevated at 24 hours and maintained higher than the controls until 2 days after I/R injury. In contrast, western blotting did not reveal any changes of betaig-h3 expression. Immunohistochemistry showed that labeling of betaig-h3 was seen at the basement membranes of proximal tubule cells mainly located at the medullary ray (S3 segment) in both groups. Following I/R injury, the labeling was also seen in the basement membrane of injured or regenerated proximal tubular epithelial cells. Within 24 hours, urinary betaig-h3 was significantly increased at 4 hours after I/R injury. Importantly, the urinary appearance of betaig-h3 preceded that of N-acetyl-beta-D-glucosaminidase. CONCLUSION: These results suggest that endogenous renal betaig-h3 may serve to promote tissue regeneration in I/R injury and urinary betaig-h3 could be used as an early and sensitive marker demonstrating I/R injury.