The glycosylated transmembrane
protein CD147/
basigin, also known as extracellular matrix
metalloproteinase (
MMP) inducer (
EMMPRIN), contributes to cell survival, migration and
cancer invasion. In normal kidneys, high expression of CD147 is detected only in the basolateral side of tubular epithelial cells (TECs). The pathophysiological roles of CD147 in the kidneys are diverse, ranging from involvement in the occurrence of
acute kidney injury (AKI) that is frequently accompanied by
ischemia,
inflammation and a loss of self-tolerance to the progression of
chronic kidney disease (CKD) that is caused by an imbalance in
extracellular matrix protein turnover. In AKI induced by
ischemia, it is the CD147 on neutrophils, rather than that on TECs, that coordinately participates in massive neutrophil recruitment via acting as a physiological
ligand for
E-selectin, which is specifically enhanced in the endothelium upon inflammatory stimulation. In the CKD that follows AKI, a molecular circuit involving CD147,
MMPs and
transforming growth factor-β may be involved in the pathogenesis of progressive
fibrosis through
hyaluronan production and macrophage infiltration. Whereas CD147 thus plays deleterious roles in ischemic and fibrotic kidney
injuries, CD147 expression on lymphocytes might decrease the disease activity of
lupus nephritis (LN) by functioning as a potential negative regulator of the extraordinary proliferation of lymphocytes that occurs in this disease. In line with these basic studies, our clinical data indicate the potential of plasma CD147 to function as a critical
biomarker for both ischemic AKI and LN. CD147 is also involved in crosstalk between the kidneys and distant organs, which may be mediated by
chemotactic cytokines that are derived from circulating inflammatory cells and damaged organs. Disruption of such a vicious chain reaction involving CD147 would therefore be required in order to overcome
kidney diseases. Multidisciplinary research regarding CD147 functions may open a new avenue for targeting
therapeutics for
kidney diseases.