PMID- 19357234
OWN - NLM
STAT- MEDLINE
DCOM- 20090709
LR  - 20211203
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 296
IP  - 6
DP  - 2009 Jun
TI  - Smad2 and 3 transcription factors control muscle mass in adulthood.
PG  - C1248-57
LID - 10.1152/ajpcell.00104.2009 [doi]
AB  - Loss of muscle mass occurs in a variety of diseases, including cancer, chronic 
      heart failure, aquired immunodeficiency syndrome, diabetes, and renal failure, 
      often aggravating pathological progression. Preventing muscle wasting by 
      promoting muscle growth has been proposed as a possible therapeutic approach. 
      Myostatin is an important negative modulator of muscle growth during myogenesis, 
      and myostatin inhibitors are attractive drug targets. However, the role of the 
      myostatin pathway in adulthood and the transcription factors involved in the 
      signaling are unclear. Moreover, recent results confirm that other transforming 
      growth factor-beta (TGF-beta) members control muscle mass. Using genetic tools, 
      we perturbed this pathway in adult myofibers, in vivo, to characterize the 
      downstream targets and their ability to control muscle mass. Smad2 and Smad3 are 
      the transcription factors downstream of myostatin/TGF-beta and induce an atrophy 
      program that is muscle RING-finger protein 1 (MuRF1) independent. Furthermore, 
      Smad2/3 inhibition promotes muscle hypertrophy independent of satellite cells but 
      partially dependent of mammalian target of rapamycin (mTOR) signaling. Thus 
      myostatin and Akt pathways cross-talk at different levels. These findings point 
      to myostatin inhibitors as good drugs to promote muscle growth during 
      rehabilitation, especially when they are combined with IGF-1-Akt activators.
FAU - Sartori, Roberta
AU  - Sartori R
AD  - Venetian Institute of Molecular Medicine, 35129 Padova, Italy.
FAU - Milan, Giulia
AU  - Milan G
FAU - Patron, Maria
AU  - Patron M
FAU - Mammucari, Cristina
AU  - Mammucari C
FAU - Blaauw, Bert
AU  - Blaauw B
FAU - Abraham, Reimar
AU  - Abraham R
FAU - Sandri, Marco
AU  - Sandri M
LA  - eng
GR  - TCP04009/TI_/Telethon/Italy
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090408
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Carrier Proteins)
RN  - 0 (Mstn protein, mouse)
RN  - 0 (Muscle Proteins)
RN  - 0 (Myostatin)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - 0 (Smad2 Protein)
RN  - 0 (Smad2 protein, mouse)
RN  - 0 (Smad3 Protein)
RN  - 0 (Smad3 protein, mouse)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Tripartite Motif Proteins)
RN  - EC 2.3.2.27 (Trim63 protein, mouse)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type I)
RN  - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type II)
SB  - IM
CIN - Am J Physiol Cell Physiol. 2009 Jun;296(6):C1245-7. PMID: 19357232
MH  - Age Factors
MH  - Animals
MH  - Carrier Proteins/metabolism
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Hypertrophy
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Muscle Denervation
MH  - *Muscle Development
MH  - Muscle Proteins/metabolism
MH  - Muscle, Skeletal/innervation/*metabolism/pathology/physiopathology
MH  - Muscular Atrophy/*metabolism/pathology/physiopathology/prevention & control
MH  - Mutation
MH  - Myostatin/metabolism
MH  - Phosphorylation
MH  - Phosphotransferases (Alcohol Group Acceptor)/metabolism
MH  - Protein Serine-Threonine Kinases/genetics/metabolism
MH  - Proto-Oncogene Proteins c-akt/genetics/metabolism
MH  - RNA Interference
MH  - RNA, Small Interfering/metabolism
MH  - Receptor, Transforming Growth Factor-beta Type I
MH  - Receptor, Transforming Growth Factor-beta Type II
MH  - Receptors, Transforming Growth Factor beta/genetics/metabolism
MH  - Sciatic Nerve/surgery
MH  - *Signal Transduction
MH  - Smad2 Protein/*metabolism
MH  - Smad3 Protein/*metabolism
MH  - TOR Serine-Threonine Kinases
MH  - Transfection
MH  - Transforming Growth Factor beta/metabolism
MH  - Tripartite Motif Proteins
MH  - Ubiquitin-Protein Ligases/metabolism
EDAT- 2009/04/10 09:00
MHDA- 2009/07/10 09:00
CRDT- 2009/04/10 09:00
PHST- 2009/04/10 09:00 [entrez]
PHST- 2009/04/10 09:00 [pubmed]
PHST- 2009/07/10 09:00 [medline]
AID - 00104.2009 [pii]
AID - 10.1152/ajpcell.00104.2009 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2009 Jun;296(6):C1248-57. doi: 
      10.1152/ajpcell.00104.2009. Epub 2009 Apr 8.