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Title: EXPRESSION OF THE TGF-BETA FAMILY OF LIGANDS IS DEVELOPMENTALLY REGULATED IN SKELETAL MUSCLE OF NEONATAL RATS

Author
item Suryawan, Agus
item FRANK, JASON - BAYLOR COLL OF MEDICINE
item NGUYEN, HANH - BAYLOR COLL OF MEDICINE
item Davis, Teresa

Submitted to: Pediatric Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/16/2005
Publication Date: 2/1/2006
Citation: Suryawan, A., Frank, J.W., Nguyen, H.V., Davis, T.A. 2006. Expression of the TGF-Beta family of ligands is developmentally regulated in skeletal muscle of neonatal rats. Pediatric Research. 59(2):175-179.

Interpretive Summary: The transforming growth factor-Beta (TGF-Beta) is a family of growth factors that regulate different aspect of animal growth, including skeletal muscle growth. However, the role of these growth factors on regulation of muscle growth during the early period, after birth, has not been evaluated. From this study we found that the amount of growth factors that inhibit muscle growth is lower in muscles of young pigs. In contrast, the amount of growth factors that stimulate muscle growth is higher in muscles of young pigs. In summary, skeletal muscle from young pigs grows faster, partly due to lower inhibition and higher stimulation of these growth factors.

Technical Abstract: To dissect the possible role of the transforming growth factor-beta (TGF-beta) family in the regulation of skeletal muscle growth during the early postnatal period, the protein abundances of the TGF-beta family and their correlation with protein synthesis were determined in skeletal muscle of neonatal rats. To obtain direct evidence of the role of these growth factors in the regulation of protein synthesis, the TGF-beta inhibitor follistatin was infused into 10-d-old rats for 11 d, and protein synthesis and phosphorylation of S6 kinase 1 (S6K1) and ribosomal protein (rpS6) were measured. TGF-beta2 abundance and protein synthesis in muscle decreased with development and were positively correlated. The abundances of bone morphogenetic protein 2 (BMP-2), BMP-7, and myostatin increased with development and were negatively correlated with protein synthesis. The abundances of BMP-2 and BMP-7 were positively correlated with BMP receptor IA (BMP-RIA) abundance. Activin A abundance was positively correlated with follistatin abundance and activin receptor IIB (Act-RIIB) abundance. Infusion of follistatin increased muscle protein synthesis and S6K1 and rpS6 phosphorylation. The results provide indirect and direct evidence of TGF-beta family involvement in the regulation of muscle protein synthesis during the neonatal period.