Identification of a Novel Stretch-Responsive Skeletal Muscle Gene (Smpx)

Kemp, Timothy J.; Sadusky, T.J.; Simon, Mary Alice; Brown, Robert A.; Eastwood, Mark; Sassoon, David; Coulton, Gary R.

doi:10.1006/geno.2000.6461

Cited by 46 publications

(31 citation statements)

References 38 publications

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“…genes including insulin-like growth factor I (63), fibroblast growth factor (64), myogenic regulatory growth factor (65), c-Jun (66), and smpx (67) have been reported in response to mechanical stretch in skeletal muscle cells. Vandenburgh et al (68) have shown that the activity of cyclooxygenase increases within 4 h of initiating mechanical stretch in skeletal muscle cells.…”

Section: Fig 12mentioning

confidence: 99%

Distinct Signaling Pathways Are Activated in Response to Mechanical Stress Applied Axially and Transversely to Skeletal Muscle Fibers

Kumar

Chaudhry

Reid

et al. 2002

Journal of Biological Chemistry

112

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In the diaphragm muscle we tested the hypothesis that MAP kinase signaling pathways are activated by mechanical stress and such signaling pathways are dependent on the direction in which mechanical stress is applied. Although equal magnitudes of mechanical stress were applied axially and transversely a greater level of activation of ERK1/2, p38, Raf-1, p90 RSK, Elk-1, and the DNA binding activity of AP-1 transcription factor was produced when the muscle was stretched transversely than when stretched axially. A significant up-regulation in protein tyrosine phosphorylation was observed in axially or transversely loaded diaphragm muscles and the activation of ERK1/2 was completely inhibited by genistein (protein-tyrosine kinase inhibitor). Pretreatment of muscles with wortmannin (phosphoinositide 3-kinase inhibitor), TMB-8 (antagonist of intracellular calcium release), GF109203X (PKC inhibitor), or PD98059 (MEK1/2 inhibitor) blocked the activation of ERK1/2 kinases in response to axial but not to transverse loading. On the other hand, pretreatment of muscles with protein kinase A inhibitors H-7 and KT5720 completely suppressed the activation of ERK1/2 in response to transverse loading only. Taken together with the alterations of MAP kinases and the findings of elevations of downstream transcription targets, our data are consistent with two distinct MAP kinase signal transduction pathways in response to mechanical stress.

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Section: Fig 12mentioning

confidence: 99%

Distinct Signaling Pathways Are Activated in Response to Mechanical Stress Applied Axially and Transversely to Skeletal Muscle Fibers

Kumar

Chaudhry

Reid

et al. 2002

Journal of Biological Chemistry

112

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“…The X-linked gene Chisel (Csl; also called Smpx) was first identified because of its selective expression in cardiac and skeletal muscle cells [20], and was subsequently fingered by us as a potential target of the cardiac homeodomain transcription factor Nkx2 -5 [21] and by others as a gene up-regulated in response to persistent skeletal muscle stretch [22]. The Csl gene is expressed in embryos in sub-regions of the developing heart corresponding to the future chamber myocardium, as well as in developing skeletal muscles [21,23].…”

Section: Introductionmentioning

confidence: 99%

Muscle costameric protein, Chisel/Smpx, associates with focal adhesion complexes and modulates cell spreading in vitro via a Rac1/p38 pathway

Lavulo

Harvey

2005

Experimental Cell Research

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“…It is highly conserved in mammals and is upregulated in skeletal muscle during passive stretch [11], [12]. SMPX is located to the costameres, but has not been verified to play a definite role as a mechanosensor in muscle.…”

Section: Introductionmentioning

confidence: 99%

“…SMPX has also been suggested to regulate another key phenotype in skeletal muscle: Putative binding sites for several muscle-specific transcription factors has been found in the promoter region located immediately 5′ to the Smpx gene, including MyoD and MEF-2 [11], [12], [14], indicating that SMPX could be regulated by one or both of these myogenic factors. Overexpression of SMPX in cultured C2C12 muscle cells leads to activation of the transcription factors MEF2 and NFAT in an IGF-1 dependent manner.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of SMPX in Adult Skeletal Muscle Does not Change Skeletal Muscle Fiber Type or Size

et al. 2014

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Mechanical factors such as stretch are thought to be important in the regulation of muscle phenotype. Small muscle protein X-linked (SMPX) is upregulated by stretch in skeletal muscle and has been suggested to serve both as a transcription factor and a mechanosensor, possibly giving rise to changes in both fiber size and fiber type. We have used in vivo confocal imaging to study the subcellular localization of SMPX in skeletal muscle fibers of adult rats using a SMPX-EGFP fusion protein. The fusion protein was localized predominantly in repetitive double stripes flanking the Z-disc, and was excluded from all nuclei. This localization would be consistent with SMPX being a mechanoreceptor, but not with SMPX playing a role as a transcription factor. In vivo overexpression of ectopic SMPX in skeletal muscle of adult mice gave no significant changes in fiber type distribution or cross sectional area, thus a role of SMPX in regulating muscle phenotype remains unclear.

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Identification of a Novel Stretch-Responsive Skeletal Muscle Gene (Smpx)

Cited by 46 publications

References 38 publications

Distinct Signaling Pathways Are Activated in Response to Mechanical Stress Applied Axially and Transversely to Skeletal Muscle Fibers

Distinct Signaling Pathways Are Activated in Response to Mechanical Stress Applied Axially and Transversely to Skeletal Muscle Fibers

Muscle costameric protein, Chisel/Smpx, associates with focal adhesion complexes and modulates cell spreading in vitro via a Rac1/p38 pathway

Overexpression of SMPX in Adult Skeletal Muscle Does not Change Skeletal Muscle Fiber Type or Size

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