Nephrolithiasis is a common kidney disease and one of the major causes of chronic renal insufficiency. We develop and utilize a glyoxylate induced mouse model of kidney calcium oxalate crystal deposition for studying the pharmacological effects of fasudil, a Rho associated protein kinase (ROCK) specific inhibitor, on the kidney injury and fibrosis caused by calcium oxalate crystallization and deposition. Glyoxylate was administrated intraperitoneally to C57BL/6J mice for five consecutive days to establish a mouse model of kidney calcium oxalate crystal formation and deposition. The results showed that the protein expression levels of E-cad and Pan-ck were lower, and the protein expression levels of α-SMA and Vim were higher, in the kidney tissue of the glyoxylate induced model mice compared with the control mice. The changes in protein expression were weakened when the animals were pretreated with fasudil before glyoxylate administration. Expression of ROCK, PAI-1, and p-Smad proteins in the kidney tissue increased in response to glyoxylate treatment, and the increase was eased when the animals were pretreated with fasudil. Expression of Smad2 and Smad3 in the kidney tissue remained unchanged after glyoxylate administration. Cell apoptosis and proliferation in the kidney cortex and medulla were enhanced in response to the glyoxylate induced calcium oxalate crystal formation and deposition, and fasudil pre-treatment was able to attenuate the enhancement. The results suggest that Fasudil reduces the glyoxylate induced kidney calcium crystal formation and deposition and slows down the kidney fibrogenesis caused by calcium crystal deposition. The possible mechanism may be related the regulatory effects on Rho/ROCK signal transduction and epithelial-mesenchymal transition (EMT).
Keywords: Calcium oxalate; Epithelial–mesenchymal transition; Fasudil; Fibrosis; Smad.
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