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中文摘要
翻译
项目总结:在所有已知的对抗健康肺部支气管收缩的因素中,深呼吸
英文摘要
Project summary: Among all factors known to antagonize bronchoconstriction in a healthy lung, a deep breath is among the most effective. In the asthmatic lung, however, this protective phenomenon is substantially at- tenuated and during a spontaneous asthmatic attack it is sometimes even reversed. Some have suggested that the inability of a deep breath to dilate the constricted asthmatic airway might be an important cause of ex- cessive airway narrowing. To explain these observations, our recent findings call attention to the extent to which breathing actually stretched the airway wall, i.e. the magnitude of circumferential strain that is imposed. The circumferential strain, in turn, must vary inversely as a function of two physical factors: (i) stiffness of the non-contractile elements of the cells and extracellular matrix (ECM) in the airway wall, and, (ii) force generated by the airway smooth muscle (ASM) itself. However, it has been nearly impossible to directly measure these factors and their relative contributions in the settings of the intraparenchymal human airway. In the absence of such knowledge, governing mechanisms will remain poorly elucidated and key pathophysiological insights will remain hidden. For example, in asthma, does enhanced ECM stiffness render the airway refractory to the beneficial effects of deep inspirations? Or is the disease pathophysiology dominated by aberrant ASM con- tractility? To find answers to these questions, in this foundational grant, we propose to develop novel enabling measurement technologies. Using a biomechanical approach that we have pioneered called traction force mi- croscopy (TFM), we propose in aim 1 to measure contractile forces generated by the ASM that is situated with- in intact human intraparenchymal airways and subjected to simulated breathing. We propose in aim 2 to de- velop new technology to measure in situ stiffness of extracellular matrix (ECM) components of the airway wall and to correlate local ECM stiffness with local cell-ECM borne stresses.
期刊论文(3)
专著(0)
科研奖励(0)
会议论文
DOI: 10.1242/jcs.196881
发表时间: 2017-03-01
期刊: Journal of cell science
影响因子: 4
作者: [Jiu Y, Peränen J, Schaible N, Cheng F, Eriksson JE, Krishnan R, Lappalainen P]
通讯作者: Lappalainen P
DOI: 10.1016/j.bbrc.2021.11.030
发表时间: 2022-01-01
期刊: Biochemical and biophysical research communications
影响因子: 3.1
作者: [Husain A, Khadka A, Ehrlicher A, Saint-Geniez M, Krishnan R]
通讯作者: Krishnan R
Traction Force Screening Enabled by Compliant PDMS Elastomers.
由合规 PDMS 弹性体实现牵引力筛选。
DOI: 10.1016/j.bpj.2018.02.045
发表时间: 2018
期刊: Biophysical journal
影响因子: 3.4
作者: [Yoshie,Haruka, Koushki,Newsha, Kaviani,Rosa, Tabatabaei,Mohammad, Rajendran,Kavitha, Dang,Quynh, Husain,Amjad, Yao,Sean, Li,Chuck, Sullivan,JohnK, Saint-Geniez,Magali, Krishnan,Ramaswamy, Ehrlicher,AllenJ]
通讯作者: Ehrlicher,AllenJ
Screening for inhibitors of allergen-associated airway smooth muscle contraction
Screening for inhibitors of allergen-associated airway smooth muscle contraction
Cooperative targeting of pharmacomechanical coupling and the actin cytoskeleton to regulate ASM contraction
  • 批准号:
    9983151
  • 项目类别:
  • 资助金额:
    $47.43万
  • 财政年份:
    2019
  • 负责人:
    RAMASWAMY KRISHNAN
  • 依托单位:
Cooperative targeting of pharmacomechanical coupling and the actin cytoskeleton to regulate ASM contraction
  • 批准号:
    10188621
  • 项目类别:
  • 资助金额:
    $47.01万
  • 财政年份:
    2019
  • 负责人:
    RAMASWAMY KRISHNAN
  • 依托单位:
海外基金