Evidence that calgranulin is produced by kidney cells and is an inhibitor of calcium oxalate crystallization.
Urine produced by normal human kidneys is almost always supersaturated with respect to calcium oxalate (CaOx), the most common constituent of human kidney stones. Crystallization, with risk of renal damage and kidney stones, appears to be affected by molecules in urine that retard nucleation, growth, aggregation, and renal cell adherence of CaOx. The repertoire of such molecules is incompletely known. We have purified a 28-kDa protein from urine using salt precipitation, preparative isoelectric focusing, and sizing chromatography. Amino acid composition and NH2-terminal amino sequence analysis showed complete homology to calgranulin. Calgranulin was found to be a potent inhibitor of CaOx crystal growth (44% of control) and aggregation (50% of control) in the nanomolar range. Calgranulin cDNA was cloned from a human kidney expression library. Western analysis of human and rat kidney homogenates and mRNA temporal expression from two independent renal epithelial cell lines showed that calgranulin is produced in the kidney. Given its urinary abundance and potency, calgranulin may contribute importantly to the normal urinary inhibition of crystal growth and aggregation and therefore to the renal defense against clinical stone disease.
Pillay
S N
SN
Department of Medicine, Section of Nephrology, University of Chicago, Chicago, Illinois 60637, USA.
Asplin
J R
JR
Coe
F L
FL
D000818:Animals; D015152:Blotting, Northern; D002129:Calcium Oxalate / Q000737:chemistry*; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000302:isolation & purification / Q000502:physiology; D002460:Cell Line; D003460:Crystallization; D018076:DNA, Complementary; D004589:Electrophoresis, Disc; D015180:Electrophoresis, Gel, Two-Dimensional; D015723:Gene Library; D006801:Humans; D007525:Isoelectric Focusing; D007668:Kidney / Q000378:metabolism*; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification / Q000652:urine; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification / Q000652:urine; D051381:Rats; D012016:Reference Values
D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D002129:Calcium Oxalate