Kidney injury molecule-1 is up-regulated in renal epithelial cells in response to oxalate in vitro and in renal tissues in response to hyperoxaluria in vivo
Authors: Sweaty Koul
Hari K Koul
Randall B Meacham
Lakshmipathi Khandrika
Journal: PLoS ONE (2012)
Discipline: Multidisciplinary
Keywords: Oxalate; Nephrolithiasis; Hyperoxaluria; Kidney Injury Molecule-1 (KIM-1); Renal epithelial cells
Affiliations: Signal Transduction and Molecular Urology Laboratory-Program in Urosciences, Division of Urology- Department of Surgery, School of Medicine, University of Colorado at Denver, Aurora, Colorado, United States of America.

Abstract:  Oxalate is a metabolic end product excreted by the kidney. Mild increases in urinary oxalate are most commonly associated with Nephrolithiasis. Chronically high levels of urinary oxalate, as seen in patients with primary hyperoxaluria, are driving factor for recurrent renal stones, and ultimately lead to renal failure, calcification of soft tissue and premature death. In previous studies others and we have demonstrated that high levels of oxalate promote injury of renal epithelial cells. However, methods to monitor oxalate induced renal injury are limited. In the present study we evaluated changes in expression of Kidney Injury Molecule-1 (KIM-1) in response to oxalate in human renal cells (HK2 cells) in culture and in renal tissue and urine samples in hyperoxaluric animals which mimic in vitro and in vivo models of hyper-oxaluria. Results presented, herein demonstrate that oxalate exposure resulted in increased expression of KIM-1 m RNA as well as protein in HK2 cells. These effects were rapid and concentration dependent. Using in vivo models of hyperoxaluria we observed elevated expression of KIM-1 in renal tissues of hyperoxaluric rats as compared to normal controls. The increase in KIM-1 was both at protein and mRNA level, suggesting transcriptional activation of KIM-1 in response to oxalate exposure. Interestingly, in addition to increased KIM-1 expression, we observed increased levels of the ectodomain of KIM-1 in urine collected from hyperoxaluric rats. To the best of our knowledge our studies are the first direct demonstration of regulation of KIM-1 in response to oxalate exposure in renal epithelial cells in vitro and in vivo. Our results suggest that detection of KIM-1 over-expression and measurement of the ectodomain of KIM-1 in urine may hold promise as a marker to monitor oxalate nephrotoxicity in hyperoxaluria. 

Retracted: Yes

PubPeer comments:
 Figure 2C: A possible differential splicing is observed in the Ubiqutin bands, but not at Beta-tubulin. Could authors check this, please? ![file] , 
 In response to this, we first want to apologize for our involuntary omission of image cropping in the figure 2c legend as we did in the Fig 4 legend (u201cImages (e) are cropped blots showing conditions of interest and are representative of 3 independent experimentsu201d) in the same article.u00a0 Back-up with original blots (scanned films), the composition made for the publication, and image analysis is provided in figure 1. According to our records, the lanes removed correspond to cells treated with inhibitors and do not alter our conclusions. The published image in the paper was size, grayscale and brightness contrast adjusted. We requested a corrigendum of Figure 2 legend to the editor, but the journal concluded this was not necessary, all data was correct. ![file] **Figure1. Original full scans indicating cropped areas.** ,