Increasing skeletal muscle growth after an induction of an atrophying inducing stimulus (i.e. disuse) is extremely important in various medical conditions. Skeletal muscle wasting can contribute to increased health care costs and a decreased quality of life. The proposed research would examine the mechanism that allows Leukemia Inhibitory Factor (LIF) to inducer satellite cell proliferation and the role it may play in muscle re- growth after 10 days of immobilization. This research would be novel in that it would identify a possible signaling mechanism that may regulate satellite cell proliferation and ultimately affect skeletal muscle growth. Further, the research would extend the role of a cytokine known to cause cardiac hypertrophy to skeletal muscle. This would be a completely novel finding. Pilot data that I have colleted indicates that LIF can induce myoblast proliferation, possibly by activating the NAK2-STAT2 or PI3K pathways. Also, I found that skeletal muscle expressed the LIF protein after 6 days of ambulatory recovery from 10 days of hindlimb immobilization. Therefore, it is proposed to determine which signaling cascades are necessary for LIF-indued satellite proliferation and to determine if this pathway extends to the whole animal. Identification of a cytokine and a signaling mechanism that may regulate muscle growth could lead to other counter-measures to ultimately prevent muscle wasting.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AR048514-01
Application #
6445216
Study Section
Special Emphasis Panel (ZRG1-SSS-3 (20))
Program Officer
Lymn, Richard W
Project Start
2002-03-08
Project End
2005-02-28
Budget Start
2002-03-08
Budget End
2003-02-28
Support Year
1
Fiscal Year
2002
Total Cost
$37,820
Indirect Cost
Name
University of Missouri-Columbia
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
112205955
City
Columbia
State
MO
Country
United States
Zip Code
65211
Rennie, Michael J; Wackerhage, Henning; Spangenburg, Espen E et al. (2004) Control of the size of the human muscle mass. Annu Rev Physiol 66:799-828
Machida, S; Spangenburg, E E; Booth, F W (2004) Primary rat muscle progenitor cells have decreased proliferation and myotube formation during passages. Cell Prolif 37:267-77
Spangenburg, Espen E; Bowles, Douglas K; Booth, Frank W (2004) Insulin-like growth factor-induced transcriptional activity of the skeletal alpha-actin gene is regulated by signaling mechanisms linked to voltage-gated calcium channels during myoblast differentiation. Endocrinology 145:2054-63
Morris, R Tyler; Spangenburg, Espen E; Booth, Frank W (2004) Responsiveness of cell signaling pathways during the failed 15-day regrowth of aged skeletal muscle. J Appl Physiol 96:398-404
Spangenburg, Espen E (2003) IGF-I isoforms and ageing skeletal muscle: an 'unresponsive' hypertrophy agent? J Physiol 547:2
Spangenburg, E E; Booth, F W (2003) Molecular regulation of individual skeletal muscle fibre types. Acta Physiol Scand 178:413-24
Spangenburg, Espen E; Abraha, Tsghe; Childs, Tom E et al. (2003) Skeletal muscle IGF-binding protein-3 and -5 expressions are age, muscle, and load dependent. Am J Physiol Endocrinol Metab 284:E340-50
Childs, Thomas E; Spangenburg, Espen E; Vyas, Dharmesh R et al. (2003) Temporal alterations in protein signaling cascades during recovery from muscle atrophy. Am J Physiol Cell Physiol 285:C391-8
Machida, Shuichi; Spangenburg, Espen E; Booth, Frank W (2003) Forkhead transcription factor FoxO1 transduces insulin-like growth factor's signal to p27Kip1 in primary skeletal muscle satellite cells. J Cell Physiol 196:523-31