Altered contractile phenotypes of intestinal smooth muscle in mice deficient in myosin phosphatase target subunit 1.
Altered contractile phenotypes of intestinal smooth muscle in mice deficient in myosin phosphatase target subunit 1.
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DOI：
10.1053/j.gastro.2013.02.045
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发表时间：
2013-06
期刊：
影响因子：
29.4
通讯作者：
Zhu MS
中科院分区：
文献类型：
--
作者：
He WQ;Qiao YN;Peng YJ;Zha JM;Zhang CH;Chen C;Chen CP;Wang P;Yang X;Li CJ;Kamm KE;Stull JT;Zhu MS
已提出肌球蛋白轻链磷酸酶的调节亚基MYPT 1通过调节Ca 2+依赖性肌球蛋白调节轻链的磷酸化来控制平滑肌收缩性。我们产生了平滑肌特异性MYPT 1缺失的小鼠，以研究其在肠平滑肌收缩中的生理作用。我们使用CreloxP系统建立Mypt 1-floxed小鼠，Mypt 1的启动子区和外显子1两侧有2个loxP位点。将这些小鼠与SMA-Cre转基因小鼠杂交，以产生具有平滑肌特异性MYPT 1缺失的小鼠（Mypt 1 SMKO小鼠）。通过组织学、生物化学、分子和生理学分析评估表型。年轻成年Mypt 1 SMKO小鼠体内肠蠕动正常，无组织学异常。KCl或乙酰胆碱刺激，肠平滑肌分离Mypt 1 SMKO小鼠产生强大的和增加的持续力，由于增加磷酸化的肌球蛋白调节轻链相比，从对照组小鼠的肌肉。对收缩特性的进一步分析显示，与对照小鼠的肌肉相比，力发展和松弛的速率降低，缩短速度降低。来自Mypt 1 SMKO小鼠的渗透性平滑肌纤维对Ca 2+的敏感性和收缩性增加。MYPT 1对小鼠平滑肌功能不是必需的，但调节力发展的Ca 2+敏感性，并有助于肠道阶段性收缩表型。在分离的组织中改变的收缩反应可以通过体内适应性生理反应来补偿，其中肠道运动受到用于肌球蛋白磷酸化和力发展的较低强度的平滑肌刺激的影响。
The regulatory subunit of myosin light chain phosphatase, MYPT1, has been proposed to control smooth muscle contractility by regulating phosphorylation of the Ca2+-dependent myosin regulatory light chain. We generated mice with a smooth muscle–specific deletion of MYPT1 to investigate its physiologic role in intestinal smooth muscle contraction. We used the CreloxP system to establish Mypt1-floxed mice, with the promoter region and exon 1 of Mypt1 flanked by 2 loxP sites. These mice were crossed with SMA-Cre transgenic mice to generate mice with smooth muscle–specific deletion of MYPT1 (Mypt1SMKO mice). The phenotype was assessed by histologic, biochemical, molecular, and physiologic analyses. Young adult Mypt1SMKO mice had normal intestinal motility in vivo, with no histologic abnormalities. On stimulation with KCl or acetylcholine, intestinal smooth muscles isolated from Mypt1SMKO mice produced robust and increased sustained force due to increased phosphorylation of the myosin regulatory light chain compared with muscle from control mice. Additional analyses of contractile properties showed reduced rates of force development and relaxation, and decreased shortening velocity, compared with muscle from control mice. Permeable smooth muscle fibers from Mypt1SMKO mice had increased sensitivity and contraction in response to Ca2+. MYPT1 is not essential for smooth muscle function in mice but regulates the Ca2+ sensitivity of force development and contributes to intestinal phasic contractile phenotype. Altered contractile responses in isolated tissues could be compensated by adaptive physiologic responses in vivo, where gut motility is affected by lower intensities of smooth muscle stimulation for myosin phosphorylation and force development.
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影响因子：
3.8
作者：
HORIUTI, K;SOMLYO, AV;SOMLYO, AP
通讯作者：
SOMLYO, AP
影响因子：
21.3
作者：
Babu, GJ;Loukianov, E;Periasamy, M
通讯作者：
Periasamy, M
影响因子：
--
作者：
Nakagawa, Tadashi;Misawa, Hiromi;Takaki, Miyako
通讯作者：
Takaki, Miyako
影响因子：
29.4
作者：
He, Wei-Qi;Peng, Ya-Jing;Zhu, Min-Sheng
通讯作者：
Zhu, Min-Sheng
DOI：
10.1073/pnas.0508566103
发表时间：
2006-02-14
影响因子：
11.1
作者：
Khromov, AS;Wang, H;Somlyo, AV
通讯作者：
Somlyo, AV