An Overview on Kidney Injury Molecule -1

Abstract

Kidney injury molecule 1 (KIM-1), also known as T-cell immunoglobulin mucin 1 (TIM-1), is a transmembrane glycoprotein mostly expressed by renal proximal tubular cells. The extracellular domain of KIM-1 is cleaved by matrix metalloproteinases and is present in the urine of rodents and humans after proximal tubular injury. It has been recognized as an early, sensitive and specific urinary biomarker for kidney injury, in both rodent models and in humans. In an acute setting, KIM-1 has anti-inflammatory and protective properties as it can transform epithelial cells into semiprofessional phagocytes by linking phosphatidylserine on dead cells. However, chronic overexpression in tubular cells can lead to inflammation and interstitial fibrosis. More recently, elevated circulating levels of KIM-1 in blood were associated with acute and chronic kidney damage. Beyond its capacity to serve as a receptor for virus entry (hence its other name, Hepatitis A virus cellular receptor 1), KIM-1 is also involved in immune response. Indeed, KIM-1 acts as: (i) a co-stimulatory molecule for T-cell activation, especially implicated in Th2 polarization; (ii) a pattern recognition receptor on invariant natural killer cells (iNKTs); and (iii) a regulator of B-cell proliferation and differentiation.