TI - PGC-1alpha inhibits activation of the ERK1/2 pathway in VSMCs by high glucose . AB - High glucose stimulates VSMC proliferation and migration through the activation of MAPK ERK signaling [3] , [4] . Consistent with these reports , our results show that high glucose activated ERK1/2 , a key element of the ERK MAPK pathway . Following PGC-1alpha overexpression , the ERK1/2 protein in VSMC no longer was activated by high glucose ( see Fig 6A ) , the PHOSphorylation of ERK in VSMCs transfected with Ad-PGC-1alpha decreased approximately 78% compared with that in Ad-GFP infected group under high glucose conditions . Furthermore , palmitic acid , which has been shown to stimulate PGC-1alpha expression , seemed to have little effect on ERK phosphorylaTION , but high glucose-induced PHOSphorylation of ERK almost reverted to the level of control by the addition of palmitic acid ( see Fig 6B ) . These results suggest that PGC-1alpha inhibits VSMC proliferation and migration through the inhibition of MAPK ERK pathway .