Reloading Promotes Recovery of Disuse Muscle Loss by Inhibiting TGFβ Pathway Activation in Rats After Hind Limb Suspension.
OBJECTIVE
The purpose of this paper was to study the effect of transforming growth factor beta (TGFβ) signaling pathway on reloading-mediated restoration of disuse muscle loss induced by hind limb suspension in rats.


METHODS
Rats were divided into 4 groups: control group (CON), HLS group (hind limb suspension for 2 weeks), HLS + R group (hind limb suspension for 2 weeks followed by 2 weeks of natural reloading), and HRS + E group (hind limb suspension for 2 weeks followed by 2 weeks of treadmill exercise). Body weight, and weight and protein concentration of gastrocnemius were determined. The expression of members of canonical and noncanonical TGFβ signaling pathways, including TGFβ1, myostatin (MSTN), phospho-smad2/3, phospho-mitogen-activated protein kinases (p38, JNK1/2, and extracellular signal-regulated kinase 1 [ERK1]/ERK2), as well as the corresponding downstream effectors of muscle mass-p21, Pax7, MyoD, and MyoG-was determined at protein or messenger RNA (mRNA) levels.


RESULTS
Reloading increased MyoD mRNA and restored the decreased gastrocnemius weight/body weight ratio, protein concentration of gastrocnemius, phospho-ERK2, Pax7 and the increased TGFβ1, MSTN, phospho-smad2/3, phospho-p38, phospho-JNK1/2, and p21 induced by hind limb suspension. Moreover, the effects of exercise reloading on the restoration of gastrocnemius weight/body weight ratio, TGFβ1, MSTN, phospho-smad2, phospho-p38, phospho-JNK2, Pax7, as well as the induction of MyoD mRNA were stronger than those of natural reloading.


CONCLUSIONS
Disuse muscle loss can be recovered by reloading in an intensity-dependent manner through canonical and noncanonical TGFβ signaling pathways. Pax7 and MyoD might be the effectors of TGFβ pathway in mediating the recovery effect of reloading.
From the Department of Physical Education, Foshan University, Foshan, People's Republic of China (JW); Department of Physical Education, North East Normal University, Changchun, People's Republic of China (XW); and Jilin Province Sport Research Institute, Changchun, People's Republic of China (WF).
Jinyue
J
Wang
Xiaohong
X
Wang
Weidou
W
Feng
D000818:Animals; D019417:Hindlimb Suspension; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009133:Muscular Atrophy / Q000378:metabolism; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D055435:Myostatin / Q000378:metabolism; D051761:Paired Box Transcription Factors / Q000378:metabolism; D010805:Physical Conditioning, Animal; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C525913:Mstn protein, rat; D017570:MyoD Protein; D055435:Myostatin; C530821:PAX7 protein, rat; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D053773:Transforming Growth Factor beta1; D048056:Mitogen-Activated Protein Kinase 9; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048051:p38 Mitogen-Activated Protein Kinases