FIGURE 10.

Scheme illustrating the temporal activation of class I and IIa HDACs during post-ischemic regeneration, their interplay, and the effect of class-selective DIs. A, during the early phase of this process, characterized by satellite cell activation and proliferation, class IIa HDAC is inactivated, and this allows the derepression of class IIa-dependent genes (c-fos, TERT, CycB, TNFα, HDAC1, and HDAC2). Class I HDAC activation in this phase, in turn, regulates the expression of miR-1 and 206. In the second phase of post-ischemic repair (from 14 to 21 days) characterized by terminal differentiation, class IIa is reactivated, and class I is repressed. B, effects of class I (MS275) and IIa (MC1568) DIs on muscle regeneration process during ischemia. Block of class I determines muscle atrophy and fibrosis, whereas block of class IIa induces delayed muscle maturation.