Disease relevance of Havcr1

• When rats were subjected to increasing periods (10, 20, 30, or 45 min) of bilateral ischemia, there was an increasing amount of urinary Kim-1 detected [1].
• We studied Kim-1 in a nontoxic, nonischemic, model of tubulointerstitial damage caused by acute proteinuria [2].
• The mRNA and protein for Kim-1 are expressed at very low levels in normal rodent kidney, but expression increases dramatically after injury in proximal tubule epithelial cells in postischemic rodent kidney and in humans during ischemic acute renal failure [3].
• Kim-1 expression was limited to areas with inflammation (MØ), fibrosis (alpha-smooth muscle actin), and tubular damage (osteopontin), and only occasionally with tubular dedifferentiation (vimentin) [2].

High impact information on Havcr1

• Structure and expression data suggest that KIM-1 is an epithelial cell adhesion molecule up-regulated in the cells, which are dedifferentiated and undergoing replication [4].
• Structurally, KIM-1 is a member of the immunoglobulin gene superfamily most reminiscent of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) [4].
• Kim-1 protein was found at the apical membrane of dilated nephrons [2].
• After folic acid treatment, expression of Kim-1 is present in the urine despite no significant increase in serum creatinine [3].
• In folic acid-treated kidneys, Kim-1 is clearly localized to the apical brush border of the well-differentiated proximal tubular epithelial cells [3].

Chemical compound and disease context of Havcr1

• After only 10 min of bilateral ischemia, Kim-1 levels on day 1 were 10-fold higher (5 ng/ml) than control levels, whereas plasma creatinine and BUN were not increased and there was no glycosuria, increased proteinuria, or increased urinary NAG levels [1].

Biological context of Havcr1

• The upregulation of expression of Kim-1 and its presence in the urine in response to exposure to various types of nephrotoxicants suggest that this protein may serve as a general biomarker for tubular injury and repair processes [3].

Anatomical context of Havcr1

• The following markers were used to assess the temporal aspects of renal damage: (a) urea nitrogen (BUN) and creatinine in blood serum, (b) kidney injury molecule (KIM-1) mRNA levels, and (c) tubular necrotic damage [5].

Associations of Havcr1 with chemical compounds

• Correlation between cyclosporine-induced nephrotoxicity in reduced nephron mass and expression of kidney injury molecule-1 and aquaporin-2 gene [6].
• In situ hybridization and immunohistochemistry revealed that KIM-1 is expressed in proliferating bromodeoxyuridine-positive and dedifferentiated vimentin-positive epithelial cells in regenerating proximal tubules [4].
• Kim-1 can be detected in the tissue and urine on days 1 and 2 after cisplatin administration, occurring before an increase in serum creatinine [3].
• To evaluate the utility of Kim-1 as a biomarker for other types of renal injury, we analyzed tissue and urinary expression in response to three different types of nephrotoxicants in the rat: S-(1,1,2,2-tetrafluoroethyl)-l-cysteine (TFEC), folic acid, and cisplatin [3].
• In the time-course study, serum creatinine and BUN increased significantly on 15-24 and 20-24h, respectively, and KIM-1 mRNA levels increased significantly on 6-24h [5].
• KIM-1 is the first nonmyeloid phosphatidylserine receptor identified to our knowledge that transforms epithelial cells into semiprofessional phagocytes [7].

Other interactions of Havcr1

• The expression of KIM-1 and AQP-2 was similar among the treatment groups [6].
• These include several transporters (Slc21a2, Slc15, Slc34a2), Kim 1, IGFbp-1, osteopontin, alpha-fibrinogen, and Gstalpha [8].

Analytical, diagnostic and therapeutic context of Havcr1

• Two mouse monoclonal antibodies were made against the purified ectodomain of kidney injury molecule-1 (Kim-1), and these were used to construct a sandwich Kim-1 ELISA [1].
• Kim-1 mRNA (RT-PCR, in situ hybridization), protein (IHC, Western blotting), and urinary Kim-1 (Luminex) were determined [2].
• Marked increases in Kim-1 expression were confirmed by immunoblotting in all three models [3].
• A few technologies are potentially promising, such as blood oxygen level dependent magnetic resonance imaging, positron emission tomography, and kidney injury molecule-1 detection in patients' urine [9].

References