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作 者:Yu Fu Jing-Ru Nie Peng Shang Bo Zhang Da-Wei Yan Xin Hao Hao Zhang
机构地区:[1]State Key Laboratory of Animal Biotech Breeding,China Agricultural University,Beijing 100193,China [2]College of Animal Science,Xizang Agricultural and Animal Husbandry University,Linzhi,Xizang 860000,China [3]College of Animal Science and Technology,Yunnan Agricultural University,Kunming,Yunnan 650201,China
出 处:《Zoological Research》2024年第4期951-960,共10页动物学研究(英文)
基 金:Xizang Major Science and Technology Project(XZ202101ZD0005N);Yunnan Major Science and Technology Project(202302AE090015);National Key R&D Program of China(2023ZD04044-04);National Natural Science Foundation of China(32060736)。
摘 要:Tumor necrosis factorα(TNFα)exhibits diverse biological functions;however,its regulatory roles in myogenesis are not fully understood.In the present study,we explored the function of TNFαin myoblast proliferation,differentiation,migration,and myotube fusion in primary myoblasts and C2C12 cells.To this end,we constructed TNFαmuscle-conditional knockout(TNFα-CKO)mice and compared them with flox mice to assess the effects of TNFαknockout on skeletal muscles.Results indicated that TNFα-CKO mice displayed phenotypes such as accelerated muscle development,enhanced regenerative capacity,and improved exercise endurance compared to flox mice,with no significant differences observed in major visceral organs or skeletal structure.Using label-free proteomic analysis,we found that TNFα-CKO altered the distribution of several muscle development-related proteins,such as Hira,Casz1,Casp7,Arhgap10,Gas1,Diaph1,Map3k20,Cfl2,and Igf2,in the nucleus and cytoplasm.Gene set enrichment analysis(GSEA)further revealed that TNFαdeficiency resulted in positive enrichment in oxidative phosphorylation and MyoD targets and negative enrichment in JAK-STAT signaling.These findings suggest that TNFα-CKO positively regulates muscle growth and development,possibly via these newly identified targets and pathways.
关 键 词:TNFΑ Muscle-conditional knockout MYOGENESIS REGENERATION Muscle development
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