1,2,3,4,6-penta-O-galloyl-beta-D-glucose attenuates renal cell migration, hyaluronan expression, and crystal adhesion.
Calcium oxalate monohydrate (COM) crystals bind avidly to the surface of proliferating and migrating renal endothelial cells, and oxalate-induced peroxidative injury can promote crystal attachment to renal epithelial cells. 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG), isolated from a traditional herbal remedy, inhibits vascular endothelial growth factor (VEGF) stimulated proliferation and migration of human umbilical vein endothelial cells (HUVECs) and has antioxidant activity. This study was performed to determine if PGG altered calcium oxalate monohydrate (COM) crystal adhesion to cells, perhaps via a change in cell surface properties. PGG significantly decreased COM crystal adhesion to cultured MDCK I cells at a low concentration (<10 microM) which was not cytotoxic. PGG exerted anti-adhesion effects whether cells or crystals were pre-coated. PGG also inhibited cell migration after scrape-wounding, decreased subsequent adhesion of crystals to proliferating and migrating cells, and decreased expression of the crystal binding molecule hyaluronan. These findings suggest that PGG represents a potential urolithiasis prevention compound. Anti-crystal adhesion effects appear multifaceted involving crystal coating by PGG, as well as decreased cell migration and the associated surface expression of hyaluronan. The latter represents a novel mechanism of nephrolithiasis prevention.
Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Jae-Ho
JH
Lee
Matthew
M
Yehl
Kwang Seok
KS
Ahn
Sung-Hoon
SH
Kim
John C
JC
Lieske
D000818:Animals; D002129:Calcium Oxalate / Q000737:chemistry / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006820:Hyaluronic Acid / Q000378:metabolism*; D047348:Hydrolyzable Tannins / Q000494:pharmacology* / Q000633:toxicity; D007668:Kidney / Q000166:cytology*; D014945:Wound Healing / Q000187:drug effects
D047348:Hydrolyzable Tannins; D002129:Calcium Oxalate; C435084:pentagalloylglucose; D006820:Hyaluronic Acid