Loss of HDAC11 accelerates skeletal muscle regeneration in mice

Abstract

Upon acute muscle damage, HDAC11 is involved in regeneration processes, both satellite and inflammatory cell‐dependent. HDAC11‐deficient myoblasts proliferate longer and present a delayed cell cycle exit, with sustained expression of proliferation genes at early differentiation. Differentiating HDAC11−/− myocytes express higher levels of myogenin, and regenerating myofibers show an increased size. Recruited macrophages secrete increased M1 pro‐inflammatory and M2 anti‐inflammatory cytokines that further enhance HDAC11 KO muscle regeneration capacity.

Increased Histone Acetylation and Decreased Expression of Specific Histone Deacetylases in Ultraviolet-Irradiated and Intrinsically Aged Human Skin In Vivo

“…In addition, inhibition of HDAC4 led to senescence in human fetal lung fibroblasts [23]; silencing of HDAC4 expression impaired TGFβ1-induced α-SMA expression [24]; and inhibition of HDAC4 caused increased MMP-1 expression via the JNK pathway [25], suggesting that HDAC4 might be linked to the aging process. HDAC11 has functions in regulating pro-and anti-inflammatory responses in immune cells as well as in muscle differentiation [26][27][28], but little is known about the role of HDAC11 in skin aging. Further research is warranted to assess the role of HDAC4 and HDAC11 in skin aging.…”

Recent developments of HDAC inhibitors: Emerging indications and novel molecules

“…Chondrocyte differentiation, 43 osteocyte mechanotransduction 44 Cardiac deficiency HDAC6 Neuronal differentiation 45 Viable, no visible pathology HDAC7 Cardiac remodelling, 46 neuroprotection, 47 endochondral ossification 48 Embryonic lethality due to dilatation and rupture of blood vessels HDAC9 Cardiac gene expression, 49 vascular calcification 50 Cardiac deficiency HDAC10 Immunoregulation 51 Viable Class 4 HDAC11 Immunoregulation, 52 muscle metabolism, 53 myoblast differentiation 54 Viable pharmacophore layout in these classes is comprised of the metalbinder moiety, the linker and the surface recognition domain 71 ; the surface recognition domain is further subdivided into a polar connecting unit and a hydrophobic cap. 72 This layout was originally proposed based on the X-ray crystallographic studies of an HDAC1 homologue HDLP with suberoylhydroxamic acid (SAHA) and TSA.…”

HDAC11: a multifaceted histone deacetylase with proficient fatty deacylase activity and its roles in physiological processes

“…Most of the highest HDAC11‐expressing tissues comprise terminally differentiated cells, with low proliferation rates under normal conditions [69]. Indeed, HDAC11 rarely colocalizes with the proliferation marker KI67 in developing brain or skeletal muscle [63,70], and its expression is repressed very quickly by the addition of mitogens to cell media [68,71]. In contrast, HDAC11 expression is induced in G 0 by cell cycle arrest [71] and in differentiation conditions upon cell cycle exit [68,70,72].…”

“…Indeed, HDAC11 rarely colocalizes with the proliferation marker KI67 in developing brain or skeletal muscle [63,70], and its expression is repressed very quickly by the addition of mitogens to cell media [68,71]. In contrast, HDAC11 expression is induced in G 0 by cell cycle arrest [71] and in differentiation conditions upon cell cycle exit [68,70,72]. In fact, HDAC11 was the most upregulated HDAC member during neural [68], myogenic [26,70], or osteoclast differentiation processes [73].…”

“…In contrast, HDAC11 expression is induced in G 0 by cell cycle arrest [71] and in differentiation conditions upon cell cycle exit [68,70,72]. In fact, HDAC11 was the most upregulated HDAC member during neural [68], myogenic [26,70], or osteoclast differentiation processes [73]. Further, HDAC11 expression is also highly induced during cardiomyocytes [74,75], plasma cells [76], or neutrophils differentiation [77,78].…”