Piezo-1 & 2’s role in murine intestinal muscularis cells of the SIP syncytium

压电1

基本信息

  • 批准号:
    10587233
  • 负责人:
  • 金额:
    $ 74.95万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-04-01 至 2027-01-31
  • 项目状态:
    未结题

项目摘要

This grant application aims to identify and characterize the role of Piezo in cells of the muscularis during baseline and stretched states. Bowel motility disorders and acute bouts of bowel obstruction are common clinical problems and can be severe, and we do not fully understand their mechanisms or have effective treatments. One crucial mechanism controlling bowel motility is mechanosensing, allowing each bowel segment to sense and respond to stretch. Various cell types within the intestinal muscularis control motility, sense stretch, and induce contractions. Among these cells are the components of the SIP syncytium comprised of smooth muscle cells (SMC), interstitial cells of Cajal (ICC), and PDGFRcells. These cells respond to stretch and receive inputs from enteric neurons (EN), glia, and enteroendocrine cells (EEC) that modulate SIP syncytium activity. However, the mechanism underlying the ability to sense and respond to stretch has not been thoroughly evaluated. Here we propose to investigate the role of Piezo in this process. Piezo is a relatively new calcium channel that functions as a mechanosensor in numerous cells, including those in the gut. Here, we will focus on its role in smooth muscle cells, interstitial cells of Cajal, and PDGFRcells of the small intestine. To perform these experiments, we have developed novel methods to maintain murine cells of the muscularis in an in vitro system. We will also use physiologically tunable hydrogels to examine the consequences of stretch in this setting. Finally, we will use various genetic approaches to explore the effects of mechanosensing in SIP cells of the gut. After this study, we anticipate that we will further elucidate the biomechanical and physiological consequences of disrupting a mechanosensitive channel that alters muscularis function and highlight myopathy's indirect effect on the adjacent epithelial layer to exacerbate the dysmotility further.
这项拨款申请的目的是确定和表征压电在基线和拉伸状态下肌层细胞中的作用。肠动力障碍和急性肠梗阻是常见的临床问题,可能很严重,我们还没有完全了解其机制或有效的治疗方法。控制肠运动的一个关键机制是机械感知,允许每个肠段感知和响应拉伸。 肠肌层内的各种类型的细胞控制运动,感觉拉伸,并诱导收缩。在这些细胞中,SIP合胞体的组分包括平滑肌细胞(SMC)、Cajal间质细胞(ICC)和PDGFR巨噬细胞。这些细胞响应拉伸并接收来自肠神经元(EN)、神经胶质和肠内分泌细胞(EEC)的输入,这些细胞调节SIP合胞体活性。然而,感知和响应拉伸能力的机制尚未得到彻底的评估。在这里,我们建议研究压电在这个过程中的作用。压电是一种相对较新的钙通道,在许多细胞中起着机械传感器的作用,包括肠道中的细胞。在这里,我们将重点关注其在平滑肌细胞,Cajal间质细胞和小肠PDGFR平滑肌细胞中的作用。 为了进行这些实验,我们已经开发了新的方法,以保持在体外系统中的小鼠细胞的肌层。我们还将使用生理上可调的水凝胶来检查这种情况下拉伸的后果。最后,我们将使用各种遗传方法来探索肠道SIP细胞中机械感知的影响。在这项研究之后,我们预计我们将进一步阐明破坏改变肌层功能的机械敏感通道的生物力学和生理学后果,并突出肌病对邻近上皮层的间接影响,以进一步加剧运动障碍。

项目成果

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James C Dunn其他文献

Ileal lengthening through internal distraction: A novel procedure for ultrashort bowel syndrome
通过内部牵引延长回肠:一种治疗超短肠综合征的新方法
  • DOI:
    10.1016/j.yjpso.2024.100124
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Aaron J Cunningham;Taylor Anderson;Claudia Mueller;Matias Bruzoni;James C Dunn
  • 通讯作者:
    James C Dunn
DIFFERENCES BETWEEN MALE AND FEMALE PATIENTS WITH PILONIDAL DISEASE
男性和女性藏毛病患者之间的差异
  • DOI:
  • 发表时间:
    2024
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Bill Chiu;Claire T Abrajano;Hiroyuki Shimada;Razie Yousefi;K. Dalusag;Madeline Adams;Wendy Su;Thomas Hui;Claudia Mueller;Julie Fuchs;James C Dunn
  • 通讯作者:
    James C Dunn

James C Dunn的其他文献

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{{ truncateString('James C Dunn', 18)}}的其他基金

Spring Mediated Enterogenesis
春季介导的肠发生
  • 批准号:
    10338557
  • 财政年份:
    2021
  • 资助金额:
    $ 74.95万
  • 项目类别:
Spring Mediated Enterogenesis
春季介导的肠发生
  • 批准号:
    10686194
  • 财政年份:
    2021
  • 资助金额:
    $ 74.95万
  • 项目类别:
Spring Mediated Enterogenesis
春季介导的肠发生
  • 批准号:
    10491119
  • 财政年份:
    2021
  • 资助金额:
    $ 74.95万
  • 项目类别:
Smooth Muscle Cell-Based Assesment and Therapy for Myopathic forms of CIPO
基于平滑肌细胞的 CIPO 肌病评估和治疗
  • 批准号:
    9263710
  • 财政年份:
    2017
  • 资助金额:
    $ 74.95万
  • 项目类别:
Intestinal Tissue Engineering
肠组织工程
  • 批准号:
    8290494
  • 财政年份:
    2010
  • 资助金额:
    $ 74.95万
  • 项目类别:
Intestinal Tissue Engineering
肠组织工程
  • 批准号:
    8082733
  • 财政年份:
    2010
  • 资助金额:
    $ 74.95万
  • 项目类别:
Intestinal Tissue Engineering
肠组织工程
  • 批准号:
    7782658
  • 财政年份:
    2010
  • 资助金额:
    $ 74.95万
  • 项目类别:
Intestinal Stem Cell Culture and Entero-endocrine Lineage Development
肠干细胞培养和肠内分泌谱系发育
  • 批准号:
    8495597
  • 财政年份:
    2009
  • 资助金额:
    $ 74.95万
  • 项目类别:
Intestinal Stem Cell Culture and Entero-endocrine Lineage Development
肠干细胞培养和肠内分泌谱系发育
  • 批准号:
    8700607
  • 财政年份:
    2009
  • 资助金额:
    $ 74.95万
  • 项目类别:
Intestinal Stem Cell Culture and Entero-Endocrine Lineage Development
肠道干细胞培养和肠内分泌谱系发育
  • 批准号:
    8923254
  • 财政年份:
    2009
  • 资助金额:
    $ 74.95万
  • 项目类别:
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