Modulation of proliferating renal epithelial cell affinity for calcium oxalate monohydrate crystals.
Adhesion of urinary crystals to distal tubular cells could be a critical event that triggers a cascade of responses ending in kidney stone formation. Monolayer cultures of distal nephron-derived MDCKI cells were used as a model to study crystal-cell interactions. COM crystal adhesion reached a peak 2 d after plating and progressively fell thereafter. The decline in crystal binding was accelerated by prostaglandin E(2) (PGE(2)) supplementation and delayed by blockade of PG production. Crystals avidly adhered to cells that migrated in to repair a scrape wound made in the monolayer and after a transient hypoglycemic insult. Exposure of MDCKI cells to uric acid crystals and soluble uric acid was also associated with increased crystal adhesion. Treatment of physically or hypoglycemically injured cells with trypsin or neuraminidase reduced crystal binding to baseline levels, suggesting that increased exposure of cell surface glycoproteins mediated the effect, whereas PGE(2) treatment blunted crystal binding to regenerating cells. Furthermore, when cells were grown in the presence of synthetic d-mannosamine analogues that can modify the conformation of cell surface sialoglycoconjugates, crystal binding to proliferating cells was decreased, whereas blockade of N-glycosylation with tunicamycin increased crystal adhesion to these cells. Therefore, COM crystal binding is enhanced to growing renal cells, synthesis of N-glycosylated cell surface proteins is essential to downregulate crystal binding to cells, and this response is modulated by physiologic signals such as PGE(2). Sialic acid residues seem to mediate crystal adhesion to growing cells, either directly or via linkage to other crystal-binding molecules. Subtle renal injury and subsequent nephron repair could be a factor promoting crystal adhesion and favoring calculus formation.
Farell
Gerard
G
Division of Nephrology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Huang
Erick
E
Kim
Soo Y
SY
Horstkorte
Rüdiger
R
Lieske
John C
JC
D000818:Animals; D002129:Calcium Oxalate / Q000737:chemistry / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003460:Crystallization; D015232:Dinoprostone / Q000494:pharmacology; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D007003:Hypoglycemia / Q000378:metabolism; D007668:Kidney / Q000166:cytology*; D007669:Kidney Calculi / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D000267:Tissue Adhesions; D014527:Uric Acid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
D002129:Calcium Oxalate; D014527:Uric Acid; D005947:Glucose; D015232:Dinoprostone