kn-93 and Ureteral-Obstruction

This study aimed to understand the mechanistic role of N-methyl-D-aspartate receptor (NMDAR) in acute fibrogenesis using models of in vivo ureter obstruction and in vitro TGF-β administration.. The expression of NR1 was upregulated in obstructed kidneys, while NR1 knockdown significantly reduced both interstitial volume expansion and the changes in the expression of α-smooth muscle actin, S100A4, fibronectin, COL1A1, Snail, and E-cadherin in acute RF. TGF-β1 treatment increased the elongation phenotype of HK-2 cells and the expression of membrane-located NR1 and phosphorylated CaMKII and extracellular signal-regulated kinase (ERK). MK801 and KN93 reduced CaMKII and ERK phosphorylation levels, while MK801, but not KN93, reduced the membrane NR1 signal. The levels of phosphorylated CaMKII and ERK also increased in kidneys with obstruction but were decreased by NR1 knockdown. The 4-week administration of DXM preserved renal cortex volume in kidneys with moderate ischemic-reperfusion injury.. NMDAR participates in both acute and chronic renal fibrogenesis potentially via CaMKII-induced ERK activation.

Topics: Animals; Benzylamines; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Dextromethorphan; Dizocilpine Maleate; Epithelial-Mesenchymal Transition; Excitatory Amino Acid Antagonists; Fibrosis; Gene Knockdown Techniques; Humans; In Vitro Techniques; Kidney; Kidney Tubules, Proximal; Mice; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Protein Kinase Inhibitors; Receptors, N-Methyl-D-Aspartate; Renal Insufficiency, Chronic; Reperfusion Injury; Sulfonamides; Transforming Growth Factor beta; Ureteral Obstruction