NDRG2, a novel regulator of myoblast proliferation, is regulated by anabolic and catabolic factors.
Skeletal muscle tissue undergoes adaptive changes in response to stress and the genes that control these processes are incompletely characterised. NDRG2 (N-myc downstream-regulated gene 2), a stress- and growth-related gene, was investigated in skeletal muscle growth and adaption. While NDRG2 expression levels were found to be up-regulated in both differentiated human and mouse myotubes compared with undifferentiated myoblasts, the suppression of NDRG2 in C2C12 myoblasts resulted in slowed myoblast proliferation. The increased expression levels of the cell cycle inhibitors, p21 Waf1/Cip1 and p27 Kip1, and of various muscle differentiation markers in NDRG2-deficient myoblasts indicate that a lack of NDRG2 promoted cell cycle exiting and the onset of myogenesis. Furthermore, the analysis of NDRG2 regulation in C2C12 myotubes treated with catabolic and anabolic agents and in skeletal muscle from human subjects following resistance exercise training revealed NDRG2 gene expression to be down-regulated during hypertrophic conditions, and conversely, up-regulated during muscle atrophy. Together, these data demonstrate that NDRG2 expression is highly responsive to different stress conditions in skeletal muscle and suggest that the level of NDRG2 expression may be critical to myoblast growth and differentiation.
Foletta
Victoria C
VC
Deakin University, Waurn Ponds, Australia. victoria.foletta@deakin.edu.au
Prior
Matthew J
MJ
Stupka
Nicole
N
Carey
Kate
K
Segal
David H
DH
Jones
Sharon
S
Swinton
Courtney
C
Martin
Sheree
S
Cameron-Smith
David
D
Walder
Ken R
KR
D048868:Adaptor Proteins, Signal Transducing; D000367:Age Factors; D000368:Aged; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D006984:Hypertrophy; D008297:Male; D051379:Mice; D024510:Muscle Development / Q000235:genetics; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009133:Muscular Atrophy / Q000378:metabolism* / Q000473:pathology; D032448:Myoblasts, Skeletal / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D055070:Resistance Training; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D000070584:Tripartite Motif Proteins; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D009124:Muscle Proteins; C466228:NDRG2 protein, human; C485172:Ndr2 protein, mouse; D011506:Proteins; D034741:RNA, Small Interfering; D000070584:Tripartite Motif Proteins; D025521:Tumor Suppressor Proteins; C440907:FBXO32 protein, human; D044843:SKP Cullin F-Box Protein Ligases; C440908:TRIM63 protein, human; D044767:Ubiquitin-Protein Ligases