title: APOBEC2 negatively regulates myoblast differentiation in muscle regeneration.
abstract: Recently we found that the deficiency of APOBEC2, a member of apoB mRNA editing enzyme, catalytic polypeptide-like family, leads to a diminished muscle mass and increased myofiber with centrally-located nuclei known as dystrophic phenotypes. APOBEC2 expression is predominant in skeletal and cardiac muscles and elevated exclusively at the early-differentiation phase of wild-type (WT) myoblast cultures; however the physiological significance is still un-known. Here we show that APOBEC2 is a key negative regulator of myoblast differentiation in muscle regeneration. APOBEC2-knockout (A2KO) mice myoblast cultures displayed a normal morphology of primary myotubes along with earlier increase in fusion index and higher expression levels of myosin heavy chain (MyHC), myogenin and its cooperating factor MEF2C than WT myoblasts. Similar response was observable in APOBEC2-knockdown cultures of WT myoblasts that were transfected with the specific siRNA at the differentiation phase (not proliferation phase). Importantly, cardiotoxin-injured A2KO gastrocnemius muscle provided in vivo evidence by showing larger up-regulation of neonatal MyHC and myogenin and hence earlier regeneration of myofiber structures with diminished cross-sectional areas and minimal Feret diameters. Therefore, the findings highlight a promising role for APOBEC2 in normal progression of regenerative myogenesis at the early-differentiation phase upon muscle injury.
authors.affiliation: Department of Animal and Marine Bioresource Sciences, Graduate School of Agriculture, Kyushu University, Hakozaki, Fukuoka 8128581, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ohtsubo
authors.affiliation: Department of Animal and Marine Bioresource Sciences, Graduate School of Agriculture, Kyushu University, Hakozaki, Fukuoka 8128581, Japan; Department of Bio-Productive Science, Utsunomiya University, Utsunomiya, Tochigi 3218505, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Animal and Marine Bioresource Sciences, Graduate School of Agriculture, Kyushu University, Hakozaki, Fukuoka 8128581, Japan; Department of Molecular and Developmental Biology, Kawasaki Medical School, Kurashiki, Okayama 7010192, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Animal and Marine Bioresource Sciences, Graduate School of Agriculture, Kyushu University, Hakozaki, Fukuoka 8128581, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Mizunoya
authors.affiliation: Graduate School of Agriculture, Kyushu University, Hakozaki, Fukuoka 8128581, Japan.
authors.forename: Mako
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Animal and Marine Bioresource Sciences, Graduate School of Agriculture, Kyushu University, Hakozaki, Fukuoka 8128581, Japan. Electronic address: rtatsumi@agr.kyushu-u.ac.jp.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Tatsumi
authors.affiliation: Department of Animal and Marine Bioresource Sciences, Graduate School of Agriculture, Kyushu University, Hakozaki, Fukuoka 8128581, Japan. Electronic address: ikeuchiy@agr.kyushu-u.ac.jp.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Ikeuchi
mesh_terms: D000071478:APOBEC Deaminases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D007150:Immunohistochemistry; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D054792:Muscle, Striated / Q000293:injuries / Q000502:physiology*; D032446:Myoblasts / Q000166:cytology*; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012038:Regeneration / Q000502:physiology*
chemical_list: D009124:Muscle Proteins; D034741:RNA, Small Interfering; D000071478:APOBEC Deaminases; C120388:APOBEC2 protein, human
keywords: APOBEC2; Muscle regeneration; Myoblast differentiation; Myogenin; Myotube