Objectives: To investigate whether hepatocyte growth factor (HGF) has a protective role against crystal-cell interaction and crystal deposits in a stone-forming rat model kidney. Crystal-cell interaction is an important step during the early stages of stone formation. High oxalate levels induce cell injuries and increase adhesion of calcium oxalate monohydrate (COM) crystals to renal tubular cells. HGF was initially identified as the most potent growth factor for hepatocytes and is well known as a mesenchyme-derived pleiotropic factor for various types of cells. HGF has mitogenic, morphogenic, and anti-apoptotic effects on renal tubular cells.
Methods: Madin-Darby canine kidney cells were exposed to potassium oxalate or COM crystals in the presence or absence of HGF. We measured lactate dehydrogenase activity in the medium and analyzed apoptosis by FACScan. COM crystal formation was induced by administration of 0.5% ethylene glycol in the drinking water and forced feeding of 0.5 microg of 1alpha-OH-D3 every other day to male Sprague-Dawley rats. Plasmid vector encoding HGF was transferred to stone-forming rats on day 1, and the kidneys were excised on day 8.
Results: Exposure of Madin-Darby canine kidney cells to both potassium oxalate (KOX) and COM crystals resulted in an increase in lactate dehydrogenase release and the proportion of apoptotic cells, but these effects were reduced by HGF. HGF had inhibitory activity against the adhesion of COM crystals to Madin-Darby canine kidney cells. HGF gene transfer significantly reduced crystal deposits on the renal tubules in stone-forming rats.
Conclusions: These findings suggest that HGF might play an important role in stone formation.