Breathe Well Live Well
Condition: Asthma
Intervention: Dietary Supplement: coconut oil
Sponsors: Brigham and Women’s Hospital; Harvard School of Public Health
Not yet recruiting – verified June 2016
View full post on ClinicalTrials.gov: asthma | received in the last 14 days
| Related Articles |
HB-EGF-Promoted Airway Smooth Muscle Cells and Their Progenitor Migration Contribute to Airway Smooth Muscle Remodeling in Asthmatic Mouse.
J Immunol. 2016 Jan 29;
Authors: Wang Q, Li H, Yao Y, Lu G, Wang Y, Xia D, Zhou J
Abstract
The airway smooth muscle (ASM) cells’ proliferation, migration, and their progenitor’s migration are currently regarded as causative factors for ASM remodeling in asthma. Heparin-binding epidermal growth factor (HB-EGF), a potent mitogen and chemotactic factor, could promote ASM cell proliferation through MAPK pathways. In this study, we obtained primary ASM cells and their progenitors from C57BL/6 mice and went on to explore the role of HB-EGF in these cells migration and the underlying mechanisms. We found that recombinant HB-EGF (rHB-EGF) intratracheal instillation accelerated ASM layer thickening in an OVA-induced asthmatic mouse. Modified Boyden chamber assay revealed that rHB-EGF facilitate ASM cell migration in a dose-dependent manner and ASM cells from asthmatic mice had a greater migration ability than that from normal counterparts. rHB-EGF could stimulate the phosphorylation of ERK1/2 and p38 in ASM cells but further migration assay showed that only epidermal growth factor receptor inhibitor (AG1478) or p38 inhibitor (SB203580), but not ERK1/2 inhibitor (PD98059), could inhibit rHB-EGF-mediated ASM cells migration. Actin cytoskeleton experiments exhibited that rHB-EGF could cause actin stress fibers disassembly and focal adhesions formation of ASM cells through the activation of p38. Finally, airway instillation of rHB-EGF promoted the recruitment of bone marrow-derived smooth muscle progenitor cells, which were transferred via caudal vein, migrating into the airway from the circulation. These observations demonstrated that ASM remodeling in asthma might have resulted from HB-EGF-mediated ASM cells and their progenitor cells migration, via p38 MAPK-dependent actin cytoskeleton remodeling.
PMID: 26826248 [PubMed – as supplied by publisher]
View full post on pubmed: asthma
 |
Related Articles |
MiR-23b controls TGF-?1 induced airway smooth muscle cell proliferation via TGF?R2/p-Smad3 signals.
Mol Immunol. 2015 Dec 31;70:84-93
Authors: Chen M, Huang L, Zhang W, Shi J, Lin X, Lv Z, Zhang W, Liang R, Jiang S
Abstract
BACKGROUND: Abnormal proliferation of ASM (airway smooth muscle) directly contributes to the airway remodeling during development of lung diseases such as asthma. Here we report that a specific microRNA (miR-23b) controls ASMCs proliferation through directly inhibiting TGF?R2/p-Smad3 pathway.
METHODS: The expression of miR-23b in ASMCs was detected by quantitative real-time polymerase chain reaction (RT-PCR). The effects of miR-23b on cell proliferation and apoptosis of ASMCs were assessed by transient transfection of miR-23b mimics and inhibitor. The target gene of miR-23b and the downstream pathway were further investigated.
RESULTS: Overexpression of miR-23b significantly inhibited TGF-?1-induced ASMCs proliferation and promoted apoptosis. RT-PCR and Western blotting analysis showed miR-23b negatively regulates the expression of TGF?R2 and p-Smad3 in ASMCs. Subsequent analyses demonstrated that TGF?R2 was a direct and functional target of miR-23b, which was validated by the dual luciferase reporter assay.
CONCLUSIONS: MiR-23b may function as an inhibitor of airway smooth muscle cells proliferation through inactivation of TGF?R2/p-Smad3 pathway.
PMID: 26748386 [PubMed – as supplied by publisher]
View full post on pubmed: asthma
| Related Articles |
Nuclear factor-?B mediates the phenotype switching of airway smooth muscle cells in a murine asthma model.
Int J Clin Exp Pathol. 2015;8(10):12115-28
Authors: Qiu C, Zhang J, Su M, Fan X
Abstract
Airway smooth muscle cells (ASMCs) phenotype modulation, characterized by reversible switching between contractile and proliferative phenotypes, is considered to contribute to airway proliferative diseases such as allergic asthma. Nuclear Factor-?B (NF-?B) has been reported as a key regulator for the occurrence and development of asthma. However, little is known regarding its role in ASM cell phenotypic modulation. To elucidate the role of NF-?B in regulating ASM cells phenotypic modulation, we investigated the effects of NF-?B on ASM cells contractile marker protein expression, and its impact on proliferation and apoptosis. We found that chronic asthma increased the activation of NF-?B in the primary murine ASM cells with a concomitant marked decrease in the expression of contractile phenotypic marker protein including smooth muscle alpha-actin (?-SMA). Additionally, we used the normal ASM cells under different processing to build the phenotype switching when we found the activation of NF-?B. Meanwhile, the expression of ?-SMA in asthma was significantly increased by the NF-?B blocker. NF-?B blocker also suppressed asthma mouse ASM cell proliferation and promoted apoptosis. These findings highlight a novel role for the NF-?B in murine ASM cell phenotypic modulation and provide a potential target for therapeutic intervention for asthma.
PMID: 26722396 [PubMed – in process]
View full post on pubmed: asthma
| Related Articles |
Apigenin inhibits TGF-?1-induced proliferation and migration of airway smooth muscle cells.
Int J Clin Exp Pathol. 2015;8(10):12557-63
Authors: Li LH, Lu B, Wu HK, Zhang H, Yao FF
Abstract
It is well known that the proliferation and migration of ASM cells (ASMCs) plays an important role in the pathogenesis of airway remodeling in asthma. Previous studies reported that apigenin can inhibit airway remodeling in a mouse asthma model. However, its effects on the proliferation and migration of ASMCs in asthma remain unknown. Therefore, the aim of our present study was to investigate the effects of apigenin on ASMC proliferation and migration, and explore the possible molecular mechanism. We found that apigenin inhibited transforming growth factor-?1 (TGF-?1)-induced ASMC proliferation. The cell cycle was blocked at G1/S-interphase by apigenin. It also suppressed TGF-?1-induced ASMCs migration. Furthermore, apigenin inhibited TGF-?1-induced Smad 2 and Smad 3 phosphorylation in ASMCs. Taken together, these results suggested that apigenin inhibited the proliferation and migration of TGF-?1-stimulated ASMCs by inhibiting Smad signaling pathway. These data might provide useful information for treating asthma and show that apigenin has potential for attenuating airway remodeling.
PMID: 26722444 [PubMed – in process]
View full post on pubmed: asthma
| Related Articles |
Soluble Guanylate Cyclase Modulators Blunt Hyperoxia Effects on Calcium Responses of Developing Human Airway Smooth Muscle.
Am J Physiol Lung Cell Mol Physiol. 2015 Aug 7;:ajplung.00232.2015
Authors: Britt RD, Thompson MA, Kuipers I, Stewart A, Vogel ER, Thu J, Martin RJ, Pabelick CM, Prakash YS
Abstract
Exposure to moderate hyperoxia in prematurity contributes to subsequent airway dysfunction and increases the risk of developing recurrent wheeze and asthma. The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic GMP (cGMP) axis modulates airway tone by regulating airway smooth muscle (ASM) intracellular Ca(2+) ([Ca(2+)]i) and contractility. However, the effects of hyperoxia on this axis in the context of Ca(2+)/contractility are not known. In developing human ASM, we explored the effects of novel drugs that activate sGC independent of NO, on alleviating hyperoxia (50% oxygen)-induced enhancement of Ca(2+) responses to bronchoconstrictor agonist. Treatment with BAY 41-2272 (sGC stimulator) and BAY 60-2770 (sGC activator) increased cGMP levels during exposure to 50% O2. Although 50% O2 did not alter sGC?1 and sGC?1 expression, BAY 60-2770 did increase sGC?1 expression. BAY 41-2272 and BAY 60-2770 blunted Ca(2+) responses to histamine in cells exposed to 50% O2. The effects of BAY 41-2272 and BAY 60-2770 were reversed by protein kinase G inhibition. These novel data demonstrate that BAY 41-2272 and BAY 60-2770 stimulate production of cGMP and blunt hyperoxia-induced increases in Ca(2+) responses in developing ASM. Accordingly, sGC stimulators/activators may be a useful therapeutic strategy in improving bronchodilation in preterm infants.
PMID: 26254425 [PubMed – as supplied by publisher]
View full post on pubmed: asthma
| Related Articles |
Nanotubes Connect CD4+ T Cells to Airway Smooth Muscle Cells: Novel Mechanism of T Cell Survival.
J Immunol. 2015 May 1;
Authors: Al Heialy S, Zeroual M, Farahnak S, McGovern T, Risse PA, Novali M, Lauzon AM, Roman HN, Martin JG
Abstract
Contact between airway smooth muscle (ASM) cells and activated CD4(+) T cells, a key interaction in diseases such as asthma, triggers ASM cell proliferation and enhances T cell survival. We hypothesized that direct contact between ASM and CD4(+) T cells facilitated the transfer of anti-apoptotic proteins via nanotubes, resulting in increased survival of activated CD4(+) T cells. CD4(+) T cells, isolated from PBMCs of healthy subjects, when activated and cocultured with ASM cells for 24 h, formed nanotubes that were visualized by immunofluorescence and atomic force microscopy. Cell-to-cell transfer of the fluorescent dye calcein-AM confirmed cytoplasmic communication via nanotubes. Immunoreactive B cell lymphoma 2 (Bcl-2) and induced myeloid leukemia cell differentiation protein (Mcl-1), two major anti-apoptotic proteins, were present within the nanotubes. Downregulation of Mcl-1 by small interfering RNA in ASM cells significantly increased T cell apoptosis, whereas downregulation of Bcl-2 had no effect. Transfer of GFP-tagged Mcl-1 from ASM cells to CD4(+) T cells via the nanotubes confirmed directionality of transfer. In conclusion, activated T cells communicate with ASM cells via nanotube formation. Direct transfer of Mcl-1 from ASM to CD(+) T cells via nanotubes is involved in T cell survival. This study provides a novel mechanism of survival of CD4(+) T cells that is dependent on interaction with a structural cell.
PMID: 25934863 [PubMed – as supplied by publisher]
View full post on pubmed: asthma
Harvard School of Engineering and Applied Sciences |
Harvard-made lung muscle could yield asthma insights
CNET As someone with asthma, I can tell you that it's not fun to feel as though a 200-pound man is sitting on your chest after you've just run a marathon. Up a flight of stairs. With a gag in your mouth. So when there's news about asthma research, my … Airway muscle-on-a-chip mimics asthma Muscle-on-a-chip Mimics Asthma, May Help Test Drugs |
View full post on asthma – Google News
| Related Articles |
Emergence of airway smooth muscle mechanical behaviour through dynamic reorganisation of contractile units and force transmission pathways.
J Appl Physiol (1985). 2014 Jan 30;
Authors: Brook BS
Abstract
Airway hyper-responsiveness (AHR) in asthma remains poorly understood despite significant research effort to elucidate relevant underlying mechanisms. In particular, a significant body of experimental work has focussed on the effect of tidal fluctuations on airway smooth muscle (ASM) cells, tissues, lung slices and whole airways in order to understand the bronchodilating effect of tidal breathing and deep inspirations. These studies have motivated conceptual models that involve dynamic reorganisation of both cytoskeletal components as well contractile machinery. In this paper, a biophysical model of the whole ASM cell is presented which combines (i) crossbridge cycling between actin and myosin, (ii) actin-myosin disconnectivity, under imposed length changes, to allow dynamic reconfiguration of “force transmission pathways” and (iii) dynamic parallel-to-serial transitions of contractile units within these pathways, that occur through a length fluctuation. Results of this theoretical model suggest that behaviour characteristic of experimentally observed force-length loops of maximally activated ASM strips can be explained by interactions between the three mechanisms. Crucially, both sustained disconnectivity and parallel-to-serial transitions are necessary to explain the nature of hysteresis and strain-stiffening observed experimentally. The results provide strong evidence that dynamic rearrangement of contractile machinery is a likely mechanism underlying many of the phenomena observed at timescales associated with tidal breathing. This theoretical cell-level model captures many of the salient features of mechanical behaviour observed experimentally and should provide a useful starting block for a bottom-up approach to understanding tissue-level mechanical behaviour.
PMID: 24481961 [PubMed – as supplied by publisher]
View full post on pubmed: asthma
Conditions: Heart Diseases; Lung Disease
Intervention: Other: Inspiratory Muscle Training
Sponsors: Clínica de Medicina do Exercício; Clínica de Medicina do Exercício
Completed – verified September 2013
View full post on ClinicalTrials.gov: asthma | received in the last 14 days