Kidney Injury Molecule-1 (KIM-1), a Putative Epithelial Cell Adhesion Molecule Containing a Novel Immunoglobulin Domain, Is Up-regulated in Renal Cells after Injury

Abstract

We report the identification of rat and human cDNAs for a type 1 membrane protein that contains a novel six-cysteine immunoglobulin-like domain and a mucin domain; it is named kidney injury molecule-1 (KIM-1). Structurally, KIM-1 is a member of the immunoglobulin gene superfamily most reminiscent of mucosal addressin cell adhesion molecule 1 (MAdCAM-1). Human KIM-1 exhibits homology to a monkey gene, hepatitis A virus cell receptor 1 (HAVcr-1), which was identified recently as a receptor for the hepatitis A virus. KIM-1 mRNA and protein are expressed at a low level in normal kidney but are increased dramatically in postischemic kidney. 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. 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. KIM-1 may play an important role in the restoration of the morphological integrity and function to postischemic kidney.

Focal Adhesion Kinase Signaling Mediates Acute Renal Injury Induced by Ischemia/Reperfusion

“…5 KIM-1 expression is an early marker of cellular injury that is specific for the proximal tubular cells and is induced by different types of injuries, including I/R injury. 19 Because FAK deficiency reduced I/R-caused KIM-1 up-regulation, cell proliferation elevation, as well as renal tissue damage, we anticipated that the lack of FAK also alleviates the cellular stress response that is otherwise driven by the hyperphosphorylation of FAK during reperfusion.…”

“…19 Briefly, after antigen retrieval, sections were blocked with normal goat serum (NGS; Vector Laboratories, Burlingame, CA) and incubated with primary antibody for 1 hour. Sections were labeled with biotinylated goat anti-mouse/rabbit IgG, and staining was visualized with an avidin-biotinylated horseradish peroxidase complex.…”

“…Expression of KIM-1 is absent in healthy kidney tissue but is strongly up-regulated at the brush border of proximal tubules after an ischemic insult. 19,21 KIM-1 was expressed in tubules of the OSOM and cortex of FAK loxP/loxP kidneys after ischemia, whereas in the FAK ⌬loxP/⌬loxP kidneys KIM-1 was predominantly found in the proximal tubules of the OSOM only, indicating attenuated renal injury in FAK ⌬loxP/⌬loxP animals ( Figure 3A). With the use of a semiquantitative scoring system for KIM-1 staining ( Figure 3B), we found that FAK ⌬loxP/⌬loxP kidneys had significantly less KIM-1 staining during I/R injury than FAK loxP/loxP kidneys ( Figure 3C).…”

Environmental exposure to arsenic and chromium in children is associated with kidney injury molecule-1

“…KIM-1 is a transmembrane glycoprotein expressed by the kidney proximal tubular epithelial cells early after injury, followed by cleavage of its ectodomain into the urine (Ichimura et al, 1998;Ichimura et al, 2004;Vaidya et al, 2010). KIM-1 is involved in kidney repair after AKI, promoting the clearance of apoptotic cells (Ichimura et al, 2008).…”

Novel technologies for the discovery and quantitation of biomarkers of toxicity

“…Using RDA, Ichimura et al identified the most differentially upregulated gene in the postischemic rat kidney, KIM-1, and confirmed its utility as a biomarker using immunoblot, immunostaining, and RNA in situ hybridization (Ichimura et al 1998). KIM-1 protein is shed from the proximal tubular epithelium into the urine following ischemic or toxic kidney injury, and its concentration in the urine is able to discriminate injured vs. healthy kidneys (Ichimura et al 1998).…”