SMAD2 and squamous cell intraepithelial neoplasia: Although silica instillation induced iNOS expression and p-Smad2/3 activation in both genotypes (Figures 7 and 8), iNOS and p-Smad2/3 immunoreactivity were significantly lower in SIL-KO than in SIL-WT animals (Figures 7E-G; Figures 8C, E, and G, respectively).