The Regulation Of Hepatocyte Growth Factor Receptor C-met Expression In Kidney

Hepatocyte growth factor (HGF) receptor c-met, a receptor tyrosine kinase, is encoded by c-met proto-oncogene. HGF/c-met signaling system plays an important role in cell proliferation, scattering, motility, cell survival and differentiation. As a unique receptor for HGF, The expression of c-met is inducible, transcriptionally regulated by a wide variety of cytokines as well as extracellular environmental cues, c-met is expressed in kidney, mainly in renal tubular epithelial cell. HGF/c-met signaling system plays a crucial role in the renal development, the preservation of its normal function and the repair and regeneration of kidney in disease condition. However, little is known about the regulation of c-met expression in kidney. In present study, we investigated the molecular mechanism of the regulation of c-met expression in constitutive condition, oxidative stress and in chronic renal disease respectively.We investigated firstly the expression pattern and the underlying mechanism controlling c-met expression in normal kidney and in various types of kidney cells. Immunohistochemical staining showed that c-met expression was widespread in normal mouse kidney, a pattern closely correlated with the renal expression of Spl and Sp3. in vitro, all types of kidney cells tested expressed different level of c-met which is tightly proportional to the abundance of Spl and Sp3 proteins. Both Spl and Sp3 bind to GC box located in c-met promoter. Coimmunoprecipitation suggested that Spl and Sp3 have physical interaction. Spl transfected into mIMCD-3 cells markedly increased the activity of c-met promoter. Although Sp3 activated c-met promoter, it can synergistically stimulate c-met promoter activity with Sp1. when deprivation of Sp binding to DNA with decoy Sp1 oligo or mithramycin A, the expression of c-met was inhibited significantly. We also found that c-met receptor in all types of kidney...