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

TLDR

KIM‑1 is a type‑1 membrane protein of the immunoglobulin superfamily, most similar to MAdCAM‑1 and the hepatitis A virus receptor HAVcr‑1. The study identified rat and human cDNAs encoding KIM‑1, a novel membrane protein with a six‑cysteine immunoglobulin‑like domain and a mucin domain. After ischemic injury, KIM‑1 mRNA and protein are markedly up‑regulated in regenerating proximal tubular epithelial cells, where it functions as an adhesion molecule that may help restore kidney structure and function.

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.<i>In situ</i> 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.