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

Kumar, Ashok; Chaudhry, Imran B; Reid, Michael B.; Boriek, Aladin M.

doi:10.1074/jbc.m203654200

Cited by 90 publications

(118 citation statements)

References 72 publications

(79 reference statements)

Supporting

Mentioning

111

Contrasting

Unclassified

Order By: Relevance

“…In Vitro Kinase Assay-The activation of JNK1 activity was determined by immunoprecipitation followed by in vitro kinase assays using GST-c-Jun-(1-79) proteins as a substrate as described previously (25).…”

Section: Methodsmentioning

confidence: 99%

Tumor Necrosis Factor-related Weak Inducer of Apoptosis Augments Matrix Metalloproteinase 9 (MMP-9) Production in Skeletal Muscle through the Activation of Nuclear Factor-κB-inducing Kinase and p38 Mitogen-activated Protein Kinase

Mittal

Paul

et al. 2009

Journal of Biological Chemistry

Self Cite

107

View full text Add to dashboard Cite

Destruction of skeletal muscle extracellular matrix is an important pathological consequence of many diseases involving muscle wasting. However, the underlying mechanisms leading to extracellular matrix breakdown in skeletal muscle tissues remain unknown. Using a microarray approach, we investigated the effect of tumor necrosis factor-related weak inducer of apoptosis (TWEAK), a recently identified muscle-wasting cytokine, on the expression of extracellular proteases in skeletal muscle. Among several other matrix metalloproteinases (MMPs), we found that the expression of MMP-9, a type IV collagenase, was drastically increased in myotubes in response to TWEAK. The level of MMP-9 was also higher in myofibers of TWEAK transgenic mice. TWEAK increased the activation of both classical and alternative nuclear factor-B (NF-B) signaling pathways. Inhibition of NF-B activity blocked the TWEAK-induced production of MMP-9 in myotubes. TWEAK also increased the activation of AP-1, and its inhibition attenuated the TWEAK-induced MMP-9 production. Overexpression of a kinase-dead mutant of NF-B-inducing kinase or IB kinase-␤ but not IB kinase-␣ significantly inhibited the TWEAK-induced activation of MMP-9 promoter. The activation of MMP-9 also involved upstream recruitment of TRAF2 and cIAP2 proteins. TWEAK increased the activity of ERK1/2, JNK1, and p38 MAPK. However, the inhibition of only p38 MAPK blocked the TWEAK-induced expression of MMP-9 in myotubes. Furthermore the loss of body and skeletal muscle weights, inflammation, fiber necrosis, and degradation of basement membrane around muscle fibers were significantly attenuated in Mmp9 knock-out mice on chronic administration of TWEAK protein.The study unveils a novel mechanism of skeletal muscle tissue destruction in pathological conditions.

show abstract

Section: Methodsmentioning

confidence: 99%

Tumor Necrosis Factor-related Weak Inducer of Apoptosis Augments Matrix Metalloproteinase 9 (MMP-9) Production in Skeletal Muscle through the Activation of Nuclear Factor-κB-inducing Kinase and p38 Mitogen-activated Protein Kinase

Mittal

Paul

et al. 2009

Journal of Biological Chemistry

Self Cite

107

View full text Add to dashboard Cite

show abstract

Section: Map Kinasesmentioning

confidence: 99%

“…JNK is canonically activated by inflammatory cytokines and stress and is often associated with negative or degenerative cellular processes, including apoptosis (129). Integrin and PTEN signaling do not appear to influence JNK activation directly (120), although both JNK and ERK are strongly activated by stretch and force generation in muscle (52,89,130).The p38 MAP kinase family is more closely related to JNK than ERK, and the four p38 isoforms are phosphorylated by MEK3 or MEK6 in response to similar stimuli, including cytokines and environmental stressors (123). Substrates for p38 again include many AP-1 elements and MAPKAPK, but also the small heat shock proteins (131).…”

mentioning

confidence: 99%

Mechanotransduction in skeletal muscle

Burkholder¹

2007

Front Biosci

103

View full text Add to dashboard Cite

Mechanical signals are critical to the development and maintenance of skeletal muscle, but the mechanisms that convert these shape changes to biochemical signals is not known. When a deformation is imposed on a muscle, changes in cellular and molecular conformations link the mechanical forces with biochemical signals, and the close integration of mechanical signals with electrical, metabolic, and hormonal signaling may disguise the aspect of the response that is specific to the mechanical forces. The mechanically induced conformational change may directly activate downstream signaling and may trigger messenger systems to activate signaling indirectly. Major effectors of mechanotransduction include the ubiquitous mitogen activated protein kinase (MAP) and phosphatidylinositol-3' kinase (PI-3K), which have well described receptor dependent cascades, but the chain of events leading from mechanical stimulation to biochemical cascade is not clear. This review will discuss the mechanics of biological deformation, loading of cellular and molecular structures, and some of the principal signaling mechanisms associated with mechanotransduction. KeywordsSkeletal muscle; mechanotransduction; stretch INTRODUCTIONThe detection and response to physical forces is essential to all cells, but is particularly relevant to those that play a fundamentally mechanical role. The primordial nature of the cellular interaction with the physical world suggests that its control should be highly regulated and specific, and that the response should integrate many aspects of cellular physiology. Pathways involved in detecting and producing forces in muscle overlap those involved in detecting nutrient availability (1,2), intracellular energy status (3,4), and oxidative status (5,6). The signaling pathways modulated by force, insulin and insulin-like growth factor I (IGF-I)(7), adenosine monophosphate (AMP) dependent kinase (AMPK) (8), reactive oxygen species (ROS) (9), and prostaglandins (PG) (10) seem intractably intertwined.The adaptations of skeletal muscle to mechanical signals have been widely described, and the interested reader is referred to several recent reviews (11)(12)(13)(14). The physiological increase in force generating capacity associated with activity, and the increase in flexibility associated with stretch, were recognized in antiquity, but the mechanisms by which those changes manifest are still unclear. The present intention is to consider the shape changes and forces associated with mechanical signals and juxtapose them with observed changes in biochemical signaling to determine what might contribute to the cellular perception of mechanical signals.Careful consideration of the mechanical environment is the first step to sort out that labyrinth of signaling. When one considers mechanisms by which the mechanical environment can be NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript sensed, it is common to think of "force" and "deformation" separately. Sometimes this distinction is legitimate, bu...

show abstract

“…However, the effect of acoustic pulsed energy on cell growth and the signal transduction mechanisms induced by this type of mechanical stimulation are not well understood. Previous studies have shown that mechanical stress such as stretch and shear stress can induce DNA synthesis in certain cell types and that extracellular signal-regulated kinase (ERK) 1 1/2 can be activated by mechanical stress (1)(2)(3)(4).…”

mentioning

confidence: 99%

Molecular Mechanisms of Low Intensity Pulsed Ultrasound in Human Skin Fibroblasts

Zhou

Schmelz

Seufferlein

et al. 2004

Journal of Biological Chemistry

223

161

View full text Add to dashboard Cite

Soluble factors such as polypeptide growth factors, mitogenic lipids, inflammatory cytokines, and hormones are known regulators of cell proliferation. However, the effect of mechanical stimuli on cell proliferation is less well understood. Here we examined the effect of low intensity pulsed ultrasound (US), which is used to promote wound healing, on the proliferation of primary human foreskin fibroblasts and the underlying signaling mechanisms. We show that a single 6 -11-min US stimulation increases bromodeoxyuridine incorporation. In addition, an increase in the total cell number is observed after sequential US stimulation. US induced stress fiber and focal adhesion formation via activation of Rho. We further observed that US selectively induced activation of extracellular signal-regulated kinase (ERK) 1/2. Inhibition of Rho-associated coiled-coil-containing protein kinase (ROCK) prevented US-induced ERK1/2 activation, demonstrating that the Rho/ROCK pathway is an upstream regulator of ERK activation in response to US. Consequently, activation of ROCK and MEK-1 was required for US-induced DNA synthesis. Finally, an integrin ␤ 1 blocking antibody as well as a RGD peptide prevented US-induced DNA synthesis. In addition, US slightly increased phosphorylation of Src at Tyr 416 , and Src activity was found to be required for ERK1/2 activation in response to US. In conclusion, our data demonstrate for the first time that US promotes cell proliferation via activation of integrin receptors and a Rho/ROCK/Src/ERK signaling pathway.Signal transduction mechanisms of receptor tyrosine kinase or heptahelical receptors have been studied extensively over the last years. However, the effect of acoustic pulsed energy on cell growth and the signal transduction mechanisms induced by this type of mechanical stimulation are not well understood. Previous studies have shown that mechanical stress such as stretch and shear stress can induce DNA synthesis in certain cell types and that extracellular signal-regulated kinase (ERK) 1 1/2 can be activated by mechanical stress (1-4).Low intensity pulsed ultrasound (US) is a special type of acoustic pulsed energy that is increasingly used as a supplementary therapy to promote bone and wound healing (5). US, transmitting as an acoustic pressure wave and applying mechanical stress indirectly to the tissues, has been reported to promote osteogenesis and protein synthesis, calcium uptake, and DNA synthesis in different cells (6 -9). US-induced DNA synthesis seems cell type-dependent; US promotes DNA synthesis in human osteoblasts, gingival fibroblasts, and periosteal cells (6, 8, 10), but not in chondrocytes (11,12). However, the molecular mechanisms by which US induces DNA synthesis or even cell proliferation are largely unknown.There is growing evidence that integrins are promising candidates for sensing extracellular matrix-derived mechanical stimuli and converting them into biochemical signals (13,14). Integrin-associated signaling pathways include an increase in tyrosine phosphorylation of...

show abstract

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

Cited by 90 publications

References 72 publications

Tumor Necrosis Factor-related Weak Inducer of Apoptosis Augments Matrix Metalloproteinase 9 (MMP-9) Production in Skeletal Muscle through the Activation of Nuclear Factor-κB-inducing Kinase and p38 Mitogen-activated Protein Kinase

Tumor Necrosis Factor-related Weak Inducer of Apoptosis Augments Matrix Metalloproteinase 9 (MMP-9) Production in Skeletal Muscle through the Activation of Nuclear Factor-κB-inducing Kinase and p38 Mitogen-activated Protein Kinase

Mechanotransduction in skeletal muscle

Molecular Mechanisms of Low Intensity Pulsed Ultrasound in Human Skin Fibroblasts

Contact Info

Product

Resources

About