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Published 14 April 2003. doi:10.1083/jcb.200208085
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© The Rockefeller University Press, 0021-9525/2003/4/111 $5.00
The Journal of Cell Biology, Volume 161, Number 1, 111-118


Article

Prostaglandin F2{alpha} stimulates growth of skeletal muscle cells via an NFATC2-dependent pathway

Valerie Horsley1,2 and Grace K. Pavlath2

1 Graduate Program in Biochemistry, Cell and Developmental Biology
2 Department of Pharmacology, Emory University, Atlanta, GA 30322

Address correspondence to Grace Pavlath, Emory University School of Medicine, Dept. of Pharmacology, Room 5027, O.W. Rollins Research Building, Atlanta, GA 30322. Tel.: (404) 727-3353. Fax: (404) 727-0365. E-mail: gpavlat{at}emory.edu

Skeletal muscle growth requires multiple steps to form large multinucleated muscle cells. Molecules that stimulate muscle growth may be therapeutic for muscle loss associated with aging, injury, or disease. However, few factors are known to increase muscle cell size. We demonstrate that prostaglandin F2{alpha} (PGF2{alpha}) as well as two analogues augment muscle cell size in vitro. This increased myotube size is not due to PGF2{alpha}-enhancing cell fusion that initially forms myotubes, but rather to PGF2{alpha} recruiting the fusion of cells with preexisting multinucleated cells. This growth is mediated through the PGF2{alpha} receptor (FP receptor). As the FP receptor can increase levels of intracellular calcium, the involvement of the calcium-regulated transcription factor nuclear factor of activated T cells (NFAT) in mediating PGF2{alpha}-enhanced cell growth was examined. We show that NFAT is activated by PGF2{alpha}, and the isoform NFATC2 is required for PGF2{alpha}-induced muscle cell growth and nuclear accretion, demonstrating the first intersection between prostaglandin receptor activation and NFAT signaling. Given this novel role for PGF2{alpha} in skeletal muscle cell growth, these studies raise caution that extended use of drugs that inhibit PG production, such as nonsteroidal antiinflammatory drugs, may be deleterious for muscle growth.

Key Words: FP receptor; calcium; myonuclei; cell fusion; NSAIDS


* Abbreviations used in this paper: CsA, cyclosporine A; DM, differentiation media; EMyHC, embryonic myosin heavy chain; FP receptor, PGF2{alpha} receptor; NFAT, nuclear factor of activated T cells; PG, prostaglandin; 17-phPGF2{alpha}, 17-phenyl trinor PGF2{alpha}.


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