1. Nitric oxide and vascular remodeling: Spotlight on the kidney
W. Eberhardt, J. Pfeilschifter 
Kidney International 
Volume 72, Pages S9-S16 (August 2007)
DOI: /sj.ki
Copyright © 2007 International Society of Nephrology Terms and Conditions

2. Figure 1
Mechanisms of action of NO involved in glomerular remodeling. NO inhibits in a cGMP-dependent manner the expression of the mRNA stabilizing factor HuR and this leads to an increased degradation of ARE-containing mRNAs, including that coding for MMP-9. Simultaneously, NO can activate the release of latent ECM-bound TGF-β by a protease-dependent cleavage from TGF-β-binding proteins. TGF-β binds to the TGF-β receptor and activates the Smad-signaling cascade. The association of receptor Smad proteins (R-Smads) with the Co-Smad gives rise to an active Smad transcription factor complex which specifically binds to a cognate promotor element, the ‘Smad-binding element’ (SBE), also present in the promoters of the TIMP-1 and PAI-1 genes. The increased expression and subsequent secretion of both protease inhibitors will attenuate the protease-dependent ECM turnover and thus promote the manifestation of tissue fibrosis. ADAM, a disintegrin and metalloproteinase; ARE, AU-rich element; PAs, plasminogen activators; MC, mesangial cell; R-Smads, receptor Smads.
Kidney International  , S9-S16DOI: ( /sj.ki )
Copyright © 2007 International Society of Nephrology Terms and Conditions