Mechanical strain regulates syndecan-4 expression and shedding in smooth muscle cells through differential activation of MAP kinase signaling pathways

Julien, M; Wang, Peiyi; Haller, Carolyn A.; Wen, Jing; Chaikof, Elliot L.

doi:10.1152/ajpcell.00093.2006

Cited by 20 publications

(17 citation statements)

References 39 publications

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“…The observed decrease in cell-associated syndecan-4 levels after 8 h cytomix stimulation may be the result of shedding of the newly synthesized protein as shedding continued to increase for 8 h following cytomix treatment. These findings reflect those found for the effects of mechanical strain on vascular smooth muscle cells where syndecan-4 expression peaks by 4 h but drops below baseline, unstrained levels by 24 h (26).…”

Section: Discussionsupporting

confidence: 85%

“…Various stimuli have been shown to induce syndecan shedding such as mechanical strain (26,33), insulin (46), thrombin (49), epidermal growth factor (49), and the phorbol ester PMA from a variety of cell types (15). Very recently the proinflammatory cytokines IFN␥ and TNF-␣ were also shown to stim-ulate syndecan-1 and -4 shedding from lung epithelial cells (44).…”

Section: Discussionmentioning

confidence: 99%

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Th1 cytokine-induced syndecan-4 shedding by airway smooth muscle cells is dependent on mitogen-activated protein kinases

Tan

Khalil

Tesarik

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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In asthma, airway smooth muscle (ASM) chemokine secretion can induce mast cell recruitment into the airways. The functions of the mast cell chemoattractant CXCL10, and other chemokines, are regulated by binding to heparan sulphates such as syndecan-4. This study is the first demonstration that airway smooth muscle cells (ASMC) from people with and without asthma express and shed syndecan-4 under basal conditions. Syndecan-4 shedding was enhanced by stimulation for 24 h with the Th1 cytokines interleukin-1β (IL-1β) or tumor necrosis factor-α (TNF-α), but not interferon-γ (IFNγ), nor the Th2 cytokines IL-4 and IL-13. ASMC stimulation with IL-1β, TNF-α, and IFNγ (cytomix) induced the highest level of syndecan-4 shedding. Nonasthmatic and asthmatic ASM cell-associated syndecan-4 protein expression was also increased by TNF-α or cytomix at 4-8 h, with the highest levels detected in cytomix-stimulated asthmatic cells. Cell-associated syndecan-4 levels were decreased by 24 h, whereas shedding remained elevated at 24 h, consistent with newly synthesized syndecan-4 being shed. Inhibition of ASMC matrix metalloproteinase-2 did not prevent syndecan-4 shedding, whereas inhibition of ERK MAPK activation reduced shedding from cytomix-stimulated ASMC. Although ERK inhibition had no effect on syndecan-4 mRNA levels stimulated by cytomix, it did cause an increase in cell-associated syndecan-4 levels, consistent with the shedding being inhibited. In conclusion, ASMC produce and shed syndecan-4 and although this is increased by the Th1 cytokines, the MAPK ERK only regulates shedding. ASMC syndecan-4 production during Th1 inflammatory conditions may regulate chemokine activity and mast cell recruitment to the ASM in asthma.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Th1 cytokine-induced syndecan-4 shedding by airway smooth muscle cells is dependent on mitogen-activated protein kinases

Tan

Khalil

Tesarik

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…In a normal aorta, SMC are aligned in the media of the artery, and subjected to mechanical stretch via pulsatile blood flow. Mechanical stretch was found to modulate SMC alignment, differentiation, migration survival/apoptosis as well as its secretion [26] through activating intracellular signaling pathways, including JNK [6], Rho-associated kinase/ROCK, NF-κB-inducing kinase [27], MAPK/ERK kinase (MEKK) [28] etc. Importantly, mechanical stretch induced MP production is ER stress dependent as we have previously shown that elevated mechanical stretch induces apoptosis of SMC in an ER stress-dependent fashion [4].…”

Section: Discussionmentioning

confidence: 99%

ER stress dependent microparticles derived from smooth muscle cells promote endothelial dysfunction during thoracic aortic aneurysm and dissection

Jia

Zhang

et al. 2017

Clinical Science

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The degeneration of vascular smooth muscle cell(s) (SMC) is one of the key features of thoracic aortic aneurysm and dissection (TAAD). We and others have shown that elevated endoplasmic reticulum (ER) stress causes SMC loss and TAAD formation, however, the mechanism of how SMC dysfunction contributes to intimal damage, leading to TAAD, remains to be explored. In the present study, in vitro assay demonstrated that elevated mechanical stretch (18% elongation, 3600 cycles/h) stimulated the ER stress response and microparticle(s) (MP) production from both SMC and endothelial cell(s) (EC) in a time-dependent manner. Treatment of EC with isolated MP led to anoikis, which was determined by measuring the fluorescence of the ethidium homodimer (EthD-1) and Calcein AM cultured in hydrogel-coated plates and control plates. MP stimulation of EC also up-regulated the mRNA levels of inflammatory molecules (i.e. Vascular cellular adhesion molecular-1 (VCAM-1)), intercellular adhesion molecular-1 (ICAM-1), interleukin-1β (IL-1β), and interleukin-6 (IL-6)). Use of an ER stress inhibitor or knockout of CHOP decreased mechanical stretch-induced MP production in SMC. In vivo, administration of an ER stress inhibitor or knockout of CHOP suppressed both apoptosis of EC and the infiltration of inflammatory cells. Moreover, TAAD formation was also suppressed by the administration of an ER stress inhibitor. In conclusion, our study demonstrates that elevated mechanical stretch induces MP formation in SMC leading to endothelial dysfunction, which is ER stress dependent. The inhibition of ER stress suppressed EC apoptosis, inflammation in the aorta, and TAAD development.

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“…The myocyte yield was ~90%, which was comparable between the two groups. Isolated cardiomyocytes were then cultured in a culture medium M199 supplemented with or without the α-adrenergic agonist phenylephrine (20 µM) [23] in the absence or presence of the antioxidant N-acetylcysteine (NAC, 500 µM) [24] the mixed α/β adrenergic antagonist carvedilol (100 nM) [25], the β-adrenergic antagonist propanolol (1 µM) [26], or the specific peptide inhibitor for JNK (JNKI, 2 µM) [27]. A cohort of cardiomyocytes was transfected with the SERCA2a adenovirus or the viral vector encoding the marker gene β-galactosidase (β-GAL) at the viral concentration of 10 8 pfu/ml for 36 hrs [28,29] where exposure of phenylephrine was initiated after 18 hrs.…”

Section: Methodsmentioning

confidence: 99%

Chronic social stress induces cardiomyocyte contractile dysfunction and intracellular Ca2+ derangement in rats

Turdi

Yuan

Leedy

et al. 2012

Physiology & Behavior

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Chronic psychosocial stress triggers cardiovascular diseases although underlying mechanisms are still elusive. This study examined the effect of social stress on cardiomyocyte contractile function and pathological changes in myocardium using the visible burrow system (VBS) model. Chronic social stress was induced using a mixed-sex VBS housing in adult Sprague-Dawley (SD) rats. Contractile and intracellular Ca2+ properties were evaluated in isolated cardiomyocytes including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR90), maximal velocity of shortening/relengthening (± dL/dt), Fura-2 fluorescence intensity, and intracellular Ca2+ decay. Myocardial histology was evaluated using Masson trichrome staining. Social stress led to depressed PS, ± dL/dt, shortened TPS and prolonged TR90 compared with the unstressed controls. Baseline and electrically-stimulated rise in Ca2+ were reduced whereas intracellular Ca2+ decay was delayed in stressed rats. Histological analyses exhibited overt interstitial fibrosis and cardiomyocyte hypertrophy in stressed rats. The GSH/GSSG ratio (indicative of oxidative stress status) was reduced whereas oxidative protein carbonyl formation was elevated in stressed rats. Western blot analysis showed unchanged expression of superoxide dismutase 1 (SOD1), β1-adrenoceptor (β1-AR) levels, reduced sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a) levels, and elevated phosphorylation of the stress signaling protein kinase JNK but not ERK in myocardium from stressed rats. Short-term in vitro treatment of cardiomyocytes with the stress inducer phenylephrine mimicked cell damage and intracellular Ca2+ mishandling, the effects of which were mitigated by antioxidant, JNK inhibition, carvedilol and SERCA2a adenovirus. These findings indicate that chronic social stress is detrimental to cardiac structure and function possibly via mechanisms associated with oxidative injury and intracellular Ca2+ mishandling.

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Mechanical strain regulates syndecan-4 expression and shedding in smooth muscle cells through differential activation of MAP kinase signaling pathways

Cited by 20 publications

References 39 publications

Th1 cytokine-induced syndecan-4 shedding by airway smooth muscle cells is dependent on mitogen-activated protein kinases

Th1 cytokine-induced syndecan-4 shedding by airway smooth muscle cells is dependent on mitogen-activated protein kinases

ER stress dependent microparticles derived from smooth muscle cells promote endothelial dysfunction during thoracic aortic aneurysm and dissection

Chronic social stress induces cardiomyocyte contractile dysfunction and intracellular Ca2+ derangement in rats

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