Figure 9. p21 deficiency ameliorates CS-induced airspace enlargement and lung function decline and protects against both CS- and sirtinol-induced increase in SA–β-gal activity.

(A and B) CS exposure for 6 months led to airspace enlargement in WT mice, which was attenuated in p21^–/– mice. (C) p21 deficiency protected against increased lung compliance induced by 6 months of CS exposure. (D) No alteration of R_L was observed in either WT or p21^–/– mice exposed to CS for 6 months. (E) Genetic ablation of p21 attenuated 6 months of CS-mediated increase in SA–β-gal activity in mouse lung. (F) Sirtinol (Sir) treatment further increased SA–β-gal activity in lungs of WT mice, but not P21^–/– mice, in response to 3 days of CS exposure. H&E-stained images are representative of experiments from 3 separate mice. Original magnification, ×100. Scale bar: 100 μm. SA–β-gal activity is expressed as 4-MU fluorescence normalized to protein content (see Methods). n = 3–4 per group. *P < 0.05, **P < 0.01, ^§P < 0.001 versus air; ^#P < 0.05, ^##P < 0.01 versus WT; ^†P < 0.05 versus vehicle.