Nitric oxide down-regulates connective tissue growth factor in rat mesangial cells

摘要: Nitric oxide down-regulates connective tissue growth factor in rat mesangial cells. Background (NO) exerts complex regulatory actions on cell (MC) biology, such as inhibition of proliferation, adhesion or contractility and induction apoptosis. In our previous studies the NO-donor S-nitroso-glutathione (GSNO) was found to be a potent inhibitor MC growth. This effect mediated at least part by inhibitory effects GSNO transcription early response gene-1 (Egr-1) 10 . We therefore were interested regulation gene expression after treatment with NO. Methods To identify genes that are regulated NO MC, analyzed representational difference analysis. Expression (CTGF) studied Northern Western blot analyses. Results Cultured MCs treated for 8 hours compared unstimulated CTGF mRNA down-regulated. The down-regulation dose-dependent transient, maximum seen 6 hours. parallel, protein observed Other NO-donors S-nitroso-N-acetyl-D,L-penicillamine spermine-NO showed similar effects. inducible NO-synthase TNF-α, IL-1β LPS provoked transient mRNA, an could partially overcome pretreatment NOS-inhibitor N ω -nitro-L-arginine methyl ester. NO-effect simulated stable cGMP analog 8br-cGMP, abolished blocking guanylyl cyclase NS2028. Conclusion acts strong repressor cultured MC. Thus, addition its antiproliferative effects, potentially antifibrotic activity CTGF.