Cellular Response to Stretch by Modulation of Cytoskeletal Tension in Two Distinct Phases

2011 ◽  
Author(s):  
Jennifer Mann ◽  
Raymond Lam ◽  
Jianping Fu
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cellular Response ◽  
Cell Structure ◽  
Muscle Cells ◽  
Underlying Mechanism ◽  
Dynamic Responses ◽  
Mechanistic Study ◽  
Mechanical Stimuli ◽  
External Forces

External forces are increasingly recognized as major regulators of cell structure and function, yet the underlying mechanism by which cells sense force and transduce it into intracellular biochemical signals and behavioral responses (‘mechanotransduction’) is largely undetermined. To aid in the mechanistic study of mechanotransduction, we devised a novel cell stretching device that allows for quantitative control and real-time measurement of mechanical stimuli and cellular biomechanical responses. Using this device, we studied the subcellular dynamic responses of contractile force and adhesion remodeling of vascular smooth muscle cells (VSMCs) to stretch. Our data showed that VSMCs could acutely enhance their contraction to resist rapid cell deformation, but they could also allow slow adaptive inelastic cytoskeletal reorganization in response to sustained cell stretch. Our study may help elucidate the mechanotransduction system in smooth muscle cells, and thus contribute to our understanding of pressure-induced vascular disease processes.

Femoral artery neointimal hyperplasia is reduced after wire injury in Ref-1+/− mice

2007 ◽  
Vol 292 (1) ◽  
pp. H516-H521 ◽  
Author(s):  
David L. Basi ◽  
Neeta Adhikari ◽  
Ami Mariash ◽  
Qinglu Li ◽  
Esther Kao ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Femoral Artery ◽  
Cellular Response ◽  
Fas Ligand ◽  
Neointimal Hyperplasia ◽  
Muscle Cells ◽  
Wild Type

Redox factor-1 (Ref-1) is a multifunctional protein that regulates redox, DNA repair, and the response to cell stress. We previously demonstrated that Ref-1+/− mice exhibit a significantly reduced Ref-1 mRNA and protein levels within the vasculature, which are associated with increased oxidative stress. The goal of this study was to test the hypothesis that partial loss of Ref-1 altered the cellular response to vascular injury. Fourteen days after femoral artery wire injury, we found that vessel intima-to-media ratio was significantly reduced in Ref-1+/− mice compared with that in wild-type mice ( P < 0.01). Bromodeoxyuridine labeling and transferase-mediated dUTP nick-end labeling staining at 14 days did not differ in the Ref-1+/− mice. In vitro studies found no significant changes in either serum-induced proliferation or baseline apoptosis in Ref-1+/− vascular smooth muscle cells. Exposure to Fas ligand; however, did result in increased susceptibility of Ref-1+/− vascular smooth muscle cells to apoptosis ( P < 0.001). Ref-1+/− mice exhibited an increase in circulating baseline levels of IL-10, IL-1α, and VEGF compared with those in wild-type mice but a marked impairment in these pathways in response to injury. In sum, loss of a single allele of Ref-1 is sufficient to reduce intimal lesion formation and to alter circulating cytokine and growth factor expression.

Phenotypic Modulation of Smooth Muscle Cells after Arterial Injury Is Associated with Changes in the Distribution of Laminin and Fibronectin

1997 ◽  
Vol 45 (6) ◽  
pp. 837-846 ◽  
Author(s):  
Johan Thyberg ◽  
Karin Blomgren ◽  
Joy Roy ◽  
Phan Kiet Tran ◽  
Ulf Hedin
Keyword(s):  
Smooth Muscle ◽  
Basement Membrane ◽  
Smooth Muscle Cells ◽  
Actin Filaments ◽  
Cell Structure ◽  
Muscle Cells ◽  
Arterial Injury ◽  
Internal Elastic Lamina ◽  
Contractile Phenotype

Earlier in vitro studies suggest opposing roles of laminin and fibronectin in regulation of differentiated properties of vascular smooth muscle cells. To find out if this may also be the case in vivo, we used immunoelectron microscopy to study the distribution of these proteins during formation of intimal thickening after arterial injury. In parallel, cell structure and content of smooth muscle α-actin was analyzed. The results indicate that the cells in the normal media are in a contractile phenotype with abundant α-actin filaments and an incomplete basement membrane. Within 1 week after endothelial denudation, most cells in the innermost layer of the media convert into a synthetic phenotype, as judged by loss of actin filaments, construction of a large secretory apparatus, and destruction of the basement membrane. Some of these cells migrate through fenestrae in the internal elastic lamina and invade a fibronectin-rich network deposited on its luminal surface. Within another few weeks a thick neointima forms, newly produced matrix components replace the strands of fibronectin, and a basement membrane reappears. Simultaneously, the cells resume a contractile phenotype, recognized by disappearance of secretory organelles and restoration of α-actin filaments. These findings support the notion that laminin and other basement membrane components promote the expression of a differentiated smooth muscle phenotype, whereas fibronectin stimulates the cells to adopt a proliferative and secretory phenotype.

Mechanotransduction in gastrointestinal smooth muscle cells: Role of mechanosensitive ion channels

2021 ◽  
Author(s):  
Vikram Joshi ◽  
Peter R Strege ◽  
Gianrico Farrugia ◽  
Arthur Beyder
Keyword(s):  
Smooth Muscle ◽  
Ion Channels ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Tissue Level ◽  
Cytoskeletal Proteins ◽  
Cell Junction ◽  
Mechanical Stimuli ◽  
Junction Molecules

Mechanosensation, the ability to properly sense mechanical stimuli and transduce them into physiologic responses, is an essential determinant of gastrointestinal (GI) function. Abnormalities in this process result in highly prevalent GI functional and motility disorders. In the GI tract, several cell types sense mechanical forces and transduce them into electrical signals, which elicit specific cellular responses. Some mechanosensitive cells like sensory neurons act as specialized mechanosensitive cells that detect forces and transduce signals into tissue-level physiologic reactions. Non-specialized mechanosensitive cells like smooth muscle cells (SMCs) adjust their function in response to forces. Mechanosensitive cells utilize various mechanoreceptors and mechanotransducers. Mechanoreceptors detect and convert force into electrical and biochemical signals, and mechanotransducers amplify and direct mechanoreceptor responses. Mechanoreceptors and mechanotransducers include ion channels, specialized cytoskeletal proteins, cell junction molecules, and G-protein coupled receptors. SMCs are particularly important due to their role as final effectors for motor function. Myogenic reflex-the ability of smooth muscle to contract in response to stretch rapidly-is a critical smooth muscle function. Such rapid mechanotransduction responses rely on mechano-gated and -sensitive ion channels, which alter their ion pores' opening in response to force, allowing fast electrical and Ca2+ responses. Though GI SMCs express a variety of such ion channels, their identities remain unknown. Recent advancements in electrophysiological, genetic, in vivo imaging, and multi-omic technologies broaden our understanding of how SMC mechano-gated and -sensitive ion channels regulate GI functions. This review discusses GI SMC mechanosensitivity's current developments with a particular emphasis on mechano-gated and -sensitive ion channels.

scholarly journals The antagonism of 6-shogaol in high-glucose-activated NLRP3 inflammasome and consequent calcification of human artery smooth muscle cells

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Te-Chuan Chen ◽  
Chia-Kung Yen ◽  
Ying-Chen Lu ◽  
Chung-Sheng Shi ◽  
Rong-Ze Hsieh ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Calcification ◽  
Muscle Cells ◽  
Underlying Mechanism ◽  
Cardiovascular Complications ◽  
High Concentration ◽  
Human Artery ◽  
Caspase 1 ◽  
Potential Therapeutic Role

Abstract Background Vascular calcification is the major reason for high mortality of cardiovascular complications for diabetes. Interleukin (IL)-1β has been implicated in this pathogenesis, but its precise role and clinical evidence have not been clearly identified. Hence, this study was aimed to investigate whether high concentration of glucose (HG), which mimics the hyperglycemia environment, could initiate vascular calcification through NLRP3/IL-1β inflammasome and the underlying mechanism. Recently, 6-shogaol, a major ginger derivate, has been elucidated its pharmaceutic role for various diseases. Therefore, the aims of this study also determined 6-shogaol effect in vascular calcification of HG initiation. Result Human artery smooth muscle cells (HASMCs) were used in this study. Glucose concentrations at 5 and 25 mM were defined as normal and HG status, respectively. The results showed that HG could increase the NLRP3, cleaved caspase 1, and pro/mature IL-1β levels to induce the expressions of bone-related matrix proteins and subsequent HASMC calcification. This process was regulated by Akt activation and reactive oxygen species (ROS) production. Moreover, 6-shogaol could inhibit the Akt/ROS signaling and NLRP3/caspase 1/IL-1β inflammasome and hence attenuated HASMC calcification. Conclusions This study elucidates the detailed mechanism of HG-initiated HASMC calcification through NLRP3/caspase 1/IL-1β inflammasome and indicates a potential therapeutic role of 6-shogaol in vascular calcification complication of diabetes.

scholarly journals Mechanical stretch is a highly selective regulator of gene expression in human bladder smooth muscle cells

2004 ◽  
Vol 20 (1) ◽  
pp. 36-44 ◽  
Author(s):  
Rosalyn M. Adam ◽  
Samuel H. Eaton ◽  
Carlos Estrada ◽  
Ashish Nimgaonkar ◽  
Shu-Ching Shih ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Ex Vivo ◽  
Muscle Cells ◽  
Mechanical Stimuli ◽  
Bladder Smooth Muscle ◽  
Human Bladder ◽  
Cox 2

Application of mechanical stimuli has been shown to alter gene expression in bladder smooth muscle cells (SMC). To date, only a limited number of “stretch-responsive” genes in this cell type have been reported. We employed oligonucleotide arrays to identify stretch-sensitive genes in primary culture human bladder SMC subjected to repetitive mechanical stimulation for 4 h. Differential gene expression between stretched and nonstretched cells was assessed using Significance Analysis of Microarrays (SAM). Expression of 20 out of 11,731 expressed genes (∼0.17%) was altered >2-fold following stretch, with 19 genes induced and one gene (FGF-9) repressed. Using real-time RT-PCR, we tested independently the responsiveness of 15 genes to stretch and to platelet-derived growth factor-BB (PDGF-BB), another hypertrophic stimulus for bladder SMC. In response to both stimuli, expression of 13 genes increased, 1 gene (FGF-9) decreased, and 1 gene was unchanged. Six transcripts (HB-EGF, BMP-2, COX-2, LIF, PAR-2, and FGF-9) were evaluated using an ex vivo rat model of bladder distension. HB-EGF, BMP-2, COX-2, LIF, and PAR-2 increased with bladder stretch ex vivo, whereas FGF-9 decreased, consistent with expression changes observed in vitro. In silico analysis of microarray data using the FIRED algorithm identified c-jun, AP-1, ATF-2, and neurofibromin-1 (NF-1) as potential transcriptional mediators of stretch signals. Furthermore, the promoters of 9 of 13 stretch-responsive genes contained AP-1 binding sites. These observations identify stretch as a highly selective regulator of gene expression in bladder SMC. Moreover, they suggest that mechanical and growth factor signals converge on common transcriptional regulators that include members of the AP-1 family.

scholarly journals The Pro-Proliferative Effects of Nicotine and Its Underlying Mechanism on Rat Airway Smooth Muscle Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e93508 ◽  
Author(s):  
Fang He ◽  
Bing Li ◽  
Zhuxiang Zhao ◽  
Yumin Zhou ◽  
Guoping Hu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Underlying Mechanism ◽  
Airway Smooth Muscle Cells

scholarly journals lncRNA MALAT1/miR-143 axis is a potential biomarker for in-stent restenosis and is involved in the multiplication of vascular smooth muscle cells

2021 ◽  
Vol 16 (1) ◽  
pp. 1303-1312
Author(s):  
Chen Cao ◽  
Wei Zhen ◽  
Haibin Yu ◽  
Li Zhang ◽  
Yiling Liu
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Group Versus ◽  
Muscle Cells ◽  
Underlying Mechanism ◽  
Control Group ◽  
Observation Group ◽  
Potential Biomarker

Abstract The purpose of this study is to observe the potential value and underlying mechanism of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/miR-143 axis in ISR. A total of 150 participants were enrolled, including 100 patients (observation group) with coronary heart disease who underwent stent implantation in the Department of Cardiology of our hospital between January 2018 and January 2020, and 50 healthy people (control group) concurrently underwent a physical examination. Serum MALAT1 and miR-143 levels were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Tumor necrosis factor-α (TNF-α; 10 ng/mL) induced human vascular smooth muscle cells (HVSMCs). MALAT1 increased while miR-143 decreased in the observation group versus the control group (P < 0.001). The non-restenosis group had significantly elevated MALAT1 expression while decreased miR-143 expression than the restenosis group (P < 0.001). The areas under the curves of the expression of MALAT1 and miR-143 in predicting restenosis were 0.917 and 0.881, respectively. Following si-MALAT1 transfection, HVSMC multiplication and invasiveness decreased significantly (P < 0.05). miR-143-inhibitor was observed to upregulate the luciferase activity of MALAT1-WT (P < 0.05). MALAT1 is highly expressed in patients with ISR while miR-143 is decreased, and the MALAT1/miR-143 axis is a potential pathway to modulate the multiplication and invasiveness of HVSMCs.

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