Fig. 8

siRNA knockdown of either cdkn1a or cdkn1c partially rescues proliferating cardiomyocytes in the Tg(hsp70: dn-xBrg1) heart.

(a,b) Quantitative PCR showed that nanoparticle-encapsulated siRNA efficiently decreased the RNA levels of cdkn1a and cdkn1c in wild-type hearts at 2 d.p.a., into which control and cdkn1a (a) or cdkn1c (b) siRNA were injected at 1 d.p.a. The RNA level was normalized to GAPDH (*P<0.05, ***P<0.001; data presented are mean±s.e.m.; paired Student’s t-test). (c–h) Ventricular apex amputation was performed in wild-type siblings and Tg(hsp70:dn-xBrg1) zebrafish, followed by heat shock treatment for 30 min daily from 5 to 14 d.p.a. The Mef2C⁺/BrdU⁺ double-positive cardiomyocytes were comparable in control siRNA-injected (d) and uninjected (c) hearts. Either encapsulated cdkn1a (f) or cdkn1c (g) siRNA partially rescued the ratio of Mef2C⁺/BrdU⁺ double-positive cardiomyocytes in Tg(hsp70:dn-xBrg1) hearts compared with those in uninjected control transgenic hearts (e). Scale bar, 100 μm. (h) Statistics of c–g (**P<0.01, ***P<0.001; data are mean±s.e.m.; one-way analysis of variance followed by Bonferroni’s multiple comparison test). The number (n) of hearts analysed in each group is indicated in each bar.