CRIT is expressed on podocytes in normal human kidney and upregulated in membranous nephropathy.
Complement C2 receptor inhibitor trispanning (CRIT) is a novel human complement regulatory cell surface receptor. It binds the human complement protein C2 and blocks the classical pathway of complement activation, thus protecting the cell against complement attack. CRIT expression in the kidney was analyzed by immunohistochemistry and in situ hybridization. Normal kidney and renal biopsies of patients with different nephropathies were studied. In glomeruli, CRIT protein was expressed only in podocytes. CRIT was also detected in endothelial cells of arterioles and arteries, but not of veins and peritubular and glomerular capillaries. A homogeneous and marked upregulation of CRIT was observed in podocytes in membranous nephropathy (MN). In focal and segmental glomerulosclerosis (FSGS) and minimal change disease, CRIT was downregulated in glomeruli with a loss of the staining in sclerotic lesions of FSGS. No specific changes were observed in the other nephropathies studied. However, podocytes showed in all pathologies a redistribution of CRIT in the cell bodies of 'activated' podocytes. The intensity of mRNA transcription correlated directly with the protein staining in the normal kidney and in MN. These data indicate that CRIT is expressed in the normal human kidney essentially by glomerular podocytes and arterial endothelial cells. The podocyte CRIT expression is upregulated in MN, which is in strong contrast with the known loss of podocyte complement receptor 1. CRIT might represent the last line of defense against complement aggression in MN, and the upregulation of CRIT in 'activated' podocytes might represent a similar self-defense mechanism.
Moll
S
S
Clinical Pathology, University Hospitals of Geneva and Lausanne, Geneva, Switzerland.
Lange
S
S
Mihatsch
M J
MJ
Dragic
Z
Z
Schifferli
J A
JA
Inal
J M
JM
D002352:Carrier Proteins / Q000096:biosynthesis*; D015433:Glomerulonephritis, Membranous / Q000276:immunology*; D006801:Humans; D007668:Kidney / Q000276:immunology*; D050199:Podocytes / Q000378:metabolism*; D015854:Up-Regulation
C505022:CRIT protein, human; D002352:Carrier Proteins