Circulating Smooth Muscle Progenitor Cells Could Migrate Into Airway Wall And Contribute To The Increased Airway Smooth Muscle In Rat Asthma Model

2012 ◽  
Author(s):  
Linhong Deng ◽  
Yuhui Dong ◽  
Xuemei Jiang
Keyword(s):  
Smooth Muscle ◽  
Progenitor Cells ◽  
Airway Smooth Muscle ◽  
Airway Wall ◽  
Asthma Model ◽  
Muscle Progenitor Cells

scholarly journals Different airway smooth muscle cells phenotypes are involved in intrinsic and extrinsic obstruction in guinea pig asthma model

2020 ◽  
Author(s):  
Mayra D Alvarez-Santos ◽  
Álvarez-González Marisol ◽  
Eslava-De Jesus Elizabeth ◽  
Angel González-López ◽  
Pacheco-Alba Ivonne ◽  
...  
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Guinea Pig ◽  
Airway Obstruction ◽  
Airway Smooth Muscle ◽  
Airway Wall ◽  
Asthma Model ◽  
Airway Tone ◽  
Tgf Β1

Abstract Background: Airway obstruction in asthma is driven by airway smooth muscle (ASM) contraction. Airway obstruction can be induced extrinsically by direct stimulation of ASM with contractile agonists or by indirect provocation with antigens, while the airway baseline tone is dependent on intrinsic obstruction. The ASM phenotypes involved in all types of obstruction seem to be related.Methods: To determination the associations of the ASM phenotypes involved in different types of airway obstruction, guinea pigs were sensitized to ovalbumin and repetitively challenged with antigen. At the third challenge, histamine provocation was used to evaluate airway responsiveness (AR), and lung samples were obtained to calculate the airway wall area. ASM cells from the trachea were disaggregated to determine 1) the percentage of cells that expressed transforming growth factor-β1 (TGF-β1), interleukin-13 (IL-13) and sarco-endoplasmic Ca2+ ATPase-2b (SERCA2b) by flow cytometry; 2) SERCA2B gene expression by RT-PCR; 3) the level of reduced glutathione (GSH) by ELISA; and 4) the sarcoplasmic reticulum Ca2+ refilling rate by microfluorometry. The control guinea pig group received only saline instead of ovalbumin. Comparisons were made using t-tests, and the associations were determined using Spearman correlation coefficient analysis.Results: Antigenic challenges induced airway obstruction and progressive incremental changes in airway baseline tone. The AR to histamine and the expression of TGF-β1 in ASM cells was increased in the asthma model. The airway wall mass and expression of IL-13 and SERCA2b in ASM cells were similar between groups. SERCA2B gene expression and GSH levels were reduced in the asthma group. The extent of antigen-induced airway obstruction was directly associated with ASM cell TGF-β1 expression and the degree of AR. The magnitude of AR and antigen-induced airway obstruction showed an inverse correlation with GSH levels. The airway baseline tone showed an inverse association with SERCA2b expression. No relationship was observed between direct or indirect airway obstruction and the airway tone. After caffeine withdrawal, the rate of sarcoplasmic reticulum Ca2+ refilling was similar in both groups.Conclusions: Each type of airway obstruction depends on different ASM phenotypes: 1) direct and indirect airway obstruction seems to be sensitive to the level of ASM oxidative stress; 2) indirect obstruction induced by antigen appears to be influenced by the expression of TGF-β1 in ASM; and 3) the SERCA2b expression level in ASM cells plays a role in the intrinsic airway tone.

scholarly journals Smooth Muscle Progenitor Cells: Friend or Foe in Vascular Disease?

2009 ◽  
Vol 4 (2) ◽  
pp. 131-140 ◽  
Author(s):  
Olivia Oostrom ◽  
Joost Fledderus ◽  
Dominique de Kleijn ◽  
Gerard Pasterkamp ◽  
Marianne Verhaar
Keyword(s):  
Smooth Muscle ◽  
Vascular Disease ◽  
Progenitor Cells ◽  
Muscle Progenitor Cells

Does the length dependency of airway smooth muscle force contribute to airway hyperresponsiveness?

2013 ◽  
Vol 115 (9) ◽  
pp. 1304-1315 ◽  
Author(s):  
Audrey Lee-Gosselin ◽  
Chris D. Pascoe ◽  
Christian Couture ◽  
Peter D. Paré ◽  
Ynuk Bossé
Keyword(s):  
Smooth Muscle ◽  
Computational Model ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Muscle Force ◽  
Morphological Data ◽  
Airway Wall ◽  
Airway Walls ◽  
Computational Analyses ◽  
Human Bronchi

Airway wall remodeling and lung hyperinflation are two typical features of asthma that may alter the contractility of airway smooth muscle (ASM) by affecting its operating length. The aims of this study were as follows: 1) to describe in detail the “length dependency of ASM force” in response to different spasmogens; and 2) to predict, based on morphological data and a computational model, the consequence of this length dependency of ASM force on airway responsiveness in asthmatic subjects who have both remodeled airway walls and hyperinflated lungs. Ovine tracheal ASM strips and human bronchial rings were isolated and stimulated to contract in response to increasing concentrations of spasmogens at three different lengths. Ovine tracheal strips were more sensitive and generated greater force at longer lengths in response to acetylcholine (ACh) and K+. Equipotent concentrations of ACh were approximately a log less for ASM stretched by 30% and approximately a log more for ASM shortened by 30%. Similar results were observed in human bronchi in response to methacholine. Morphometric and computational analyses predicted that the ASM of asthmatic subjects may be elongated by 6.6–10.4% (depending on airway generation) due to remodeling and/or hyperinflation, which could increase ACh-induced force by 1.8–117.8% (depending on ASM length and ACh concentration) and enhance the increased resistance to airflow by 0.4–4,432.8%. In conclusion, elongation of ASM imposed by airway wall remodeling and/or hyperinflation may allow ASM to operate at a longer length and to consequently generate more force and respond to lower concentration of spasmogens. This phenomenon could contribute to airway hyperresponsiveness.

scholarly journals Reduction of Connexin 43 Attenuates Angiogenic Effects of Human Smooth Muscle Progenitor Cells via Inactivation of Akt and NF-κB Pathway

2020 ◽  
Author(s):  
Ting-Yi Tien ◽  
Yih-Jer Wu ◽  
Cheng-Huang Su ◽  
Hsueh-Hsiao Wang ◽  
Chin-Ling Hsieh ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Progenitor Cells ◽  
Connexin 43 ◽  
Paracrine Effects ◽  
Angiogenic Potential ◽  
Junction Protein ◽  
Src Activation ◽  
Muscle Progenitor Cells

Objective: Circulating progenitor cells possess vasculogenesis property and participate in repair of vascular injury. Cx (connexin) 43—a transmembrane protein constituting gap junctions—is involved in vascular pathology. However, the role of Cx43 in smooth muscle progenitor cells (SPCs) remained unclear. Approach and Results: Human SPCs cultured from CD34 + peripheral blood mononuclear cells expressed smooth muscle cell markers, such as smooth muscle MHC (myosin heavy chain), nonmuscle MHC, calponin, and CD140B, and Cx43 was the most abundant Cx isoform. To evaluate the role of Cx43 in SPCs, short interference RNA was used to knock down Cx43 expression. Cellular activities of SPCs were reduced by Cx43 downregulation. In addition, Cx43 downregulation attenuated angiogenic potential of SPCs in hind limb ischemia mice. Protein array and ELISA of the supernatant from SPCs showed that IL (interleukin)-6, IL-8, and HGF (hepatocyte growth factor) were reduced by Cx43 downregulation. Simultaneously, Cx43 downregulation reduced the phosphorylation of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) and Akt (protein kinase B) pathway and reactivation of NF-κB and Akt using betulinic acid, and SC79 could restore the secretion of growth factors and cytokines. Moreover, FAK (focal adhesion kinase)-Src (proto-oncogene tyrosine-protein kinase Src) activation was increased by Cx43 downregulation, and inactivation of Akt–NF-κB could be restored by Src inhibitor (PP2), indicating that Akt–NF-κB inactivated by Cx43 downregulation arose from FAK-Src activation. Finally, the depressed cellular activities and secretion of SPCs after Cx43 downregulation were restored by FAK inhibitor PF-562271 or PP2. Conclusions: SPCs possess angiogenic potential to repair ischemic tissue mainly through paracrine effects. Gap junction protein Cx43 plays an important role in regulating cellular function and paracrine effects of SPCs through FAK-Src axis.

scholarly journals In vitro, in silico and in vivo study challenges the impact of bronchial thermoplasty on acute airway smooth muscle mass loss

2018 ◽  
Vol 51 (5) ◽  
pp. 1701680 ◽  
Author(s):  
Igor L. Chernyavsky ◽  
Richard J. Russell ◽  
Ruth M. Saunders ◽  
Gavin E. Morris ◽  
Rachid Berair ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Asthma Control ◽  
Muscle Mass ◽  
Airway Smooth Muscle ◽  
In Silico ◽  
Heat Distribution ◽  
Airway Wall ◽  
Epithelial Integrity

Bronchial thermoplasty is a treatment for asthma. It is currently unclear whether its histopathological impact is sufficiently explained by the proportion of airway wall that is exposed to temperatures necessary to affect cell survival.Airway smooth muscle and bronchial epithelial cells were exposed to media (37–70°C) for 10 s to mimic thermoplasty. In silico we developed a mathematical model of airway heat distribution post-thermoplasty. In vivo we determined airway smooth muscle mass and epithelial integrity pre- and post-thermoplasty in 14 patients with severe asthma.In vitro airway smooth muscle and epithelial cell number decreased significantly following the addition of media heated to ≥65°C. In silico simulations showed a heterogeneous heat distribution that was amplified in larger airways, with <10% of the airway wall heated to >60°C in airways with an inner radius of ∼4 mm. In vivo at 6 weeks post-thermoplasty, there was an improvement in asthma control (measured via Asthma Control Questionnaire-6; mean difference 0.7, 95% CI 0.1–1.3; p=0.03), airway smooth muscle mass decreased (absolute median reduction 5%, interquartile range (IQR) 0–10; p=0.03) and epithelial integrity increased (14%, IQR 6–29; p=0.007). Neither of the latter two outcomes was related to improved asthma control.Integrated in vitro and in silico modelling suggest that the reduction in airway smooth muscle post-thermoplasty cannot be fully explained by acute heating, and nor did this reduction confer a greater improvement in asthma control.

scholarly journals Modulation of TGF-β/BMP-6 expression and increased levels of circulating smooth muscle progenitor cells in a type I diabetes mouse model

2010 ◽  
Vol 9 (1) ◽  
pp. 55 ◽  
Author(s):  
Peter E Westerweel ◽  
Cindy TJ van Velthoven ◽  
Tri Q Nguyen ◽  
Krista den Ouden ◽  
Dominique PV de Kleijn ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Mouse Model ◽  
Progenitor Cells ◽  
Type I Diabetes ◽  
Type I ◽  
Muscle Progenitor Cells ◽  
Diabetes Mouse

Airway smooth muscle orientation in intraparenchymal airways

1997 ◽  
Vol 82 (1) ◽  
pp. 70-77 ◽  
Author(s):  
M. Lei ◽  
H. Ghezzo ◽  
M. F. Chen ◽  
D. H. Eidelman
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Serial Sections ◽  
Airway Wall ◽  
Transverse Axis ◽  
Mean Values ◽  
Airway Narrowing ◽  
Human Specimen ◽  
The Mean ◽  
Airway Tree

Lei, M., H. Ghezzo, M. F. Chen, and D. H. Eidelman.Airway smooth muscle orientation in intraparenchymal airways. J. Appl. Physiol. 82(1): 70–77, 1997.—Airway smooth muscle (ASM) shortening is the central event leading to bronchoconstriction. The degree to which airway narrowing occurs as a consequence of shortening is a function of both the mechanical properties of the airway wall as well as the orientation of the muscle fibers. Although the latter is theoretically important, it has not been systematically measured to date. The purpose of this study was to determine the angle of orientation of ASM (θ) in normal lungs by using a morphometric approach. We analyzed the airway tree of the left lower lobes of four cats and one human. All material was fixed with 10% buffered Formalin at a pressure of 25 cmH2O for 48 h. The fixed material was dissected along the airway tree to permit isolation of generations 4–18 in the cats and generations 5–22 in the human specimen. Each airway generation was individually embedded in paraffin. Five-micrometer-thick serial sections were cut parallel to the airway long axis and stained with hematoxylin-phloxine-saffron. Each block yielded three to five sections containing ASM. To determine θ, we measured the orientation of ASM nuclei relative to the transverse axis of the airway by using a digitizing tablet and a light microscope (×250) equipped with a drawing tube attachment. Inspection of the sections revealed extensive ASM crisscrossing without a homogeneous orientation. The θ was clustered between −20° and 20° in all airway generations and did not vary much between generations in any of the cats or in the human specimen. When θ was expressed without regard to sign, the mean values were 13.2° in the cats and 13.1° in the human. This magnitude of obliquity is not likely to result in physiologically important changes in airway length during bronchoconstriction.

Modulation of the airway smooth muscle phenotype in a murine asthma model and effects of nuclear factor-κB inhibition

2019 ◽  
Vol 56 (12) ◽  
pp. 1247-1256 ◽  
Author(s):  
Chen Qiu ◽  
Jie Li ◽  
Jian Zhang ◽  
Qi He ◽  
Lingwei Wang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Asthma Model ◽  
Murine Asthma Model
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