Loss of HDAC11 accelerates skeletal muscle regeneration in mice. (21st July 2020)

• Record Type: Journal Article
• Authors: Núñez‐Álvarez, Yaiza; Hurtado, Erica; Muñoz, Mar; García‐Tuñon, Ignacio; Rech, Gabriel E.; Pluvinet, Raquel; Sumoy, Lauro; Pendás, Alberto M.; Peinado, Miguel A.; Suelves, Mònica
• Is Part Of: FEBS journal. Volume 288:Number 4(2021)
• Page Start: 1201
• Page End: 1223
• Publication Date: 2020-07-21
• Subjects: cell cycle exit -- HDAC11 -- IL‐10 -- satellite cells -- skeletal muscle regeneration; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.15468
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : Histone deacetylase 11 (HDAC11) is the latest identified member of the histone deacetylase family of enzymes. It is highly expressed in brain, heart, testis, kidney, and skeletal muscle, although its role in these tissues is poorly understood. Here, we investigate for the first time the consequences of HDAC11 genetic impairment on skeletal muscle regeneration, a process principally dependent on its resident stem cells (satellite cells) in coordination with infiltrating immune cells and stromal cells. Our results show that HDAC11 is dispensable for adult muscle growth and establishment of the satellite cell population, while HDAC11 deficiency advances the regeneration process in response to muscle injury. This effect is not caused by differences in satellite cell activation or proliferation upon injury, but rather by an enhanced capacity of satellite cells to differentiate at early regeneration stages in the absence of HDAC11. Infiltrating HDAC11‐deficient macrophages could also contribute to this accelerated muscle regenerative process by prematurely producing high levels of IL‐10, a cytokine known to promote myoblast differentiation. Altogether, our results show that HDAC11 depletion advances skeletal muscle regeneration and this finding may have potential implications for designing new strategies for muscle pathologies coursing with chronic damage. Database: Data were deposited in NCBI's Gene Expression Omnibus accessible through GEO Series accession number GSE147423 . 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.