Decreased expression of smooth muscle α-actin results in decreased contractile function of the mouse bladder
Decreased expression of smooth muscle α-actin results in decreased contractile function of the mouse bladder
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DOI：
10.1097/01.ju.0000139874.48574.1b
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发表时间：
2004-10-01
影响因子：
6.6
通讯作者：
Kropp, BP
中科院分区：
文献类型：
--
作者：
Zimmerman, RA;Tomasek, JJ;Kropp, BP
目的：平滑肌α-肌动蛋白(SMalphaA)是小鼠膀胱功能收缩的重要肌动蛋白亚型。SmaA表达的改变与多种膀胱病理状态有关。最近，一只SMalphaA缺失的小鼠被产生，观察到野生型和SmaA缺失的小鼠在血管张力和收缩能力上的差异，表明血管平滑肌功能发生了变化。材料和方法：采用逆转录聚合酶链式反应、Western blotting和免疫组织化学染色等方法证实SMalphaA基因缺失小鼠膀胱中SMalphaA基因的转录和蛋白的缺失。通过电场刺激(EFS)以及化学激动剂和拮抗剂(包括KCl、卡巴胆碱、阿托品和河豚毒素)的作用，比较了野生型和SMalphaA基因缺失小鼠膀胱环的体外收缩性能。结果：在SMAA缺失小鼠的膀胱中没有检测到SMalphaA的转录和蛋白表达。9只野生型和9只SMalphaA缺失型小鼠被用于收缩性能研究。与野生型小鼠相比，SMalphaA缺失型小鼠在KCl后对EFS的反应产生的膀胱力量显著减少。同样，SMalphaA缺失小鼠的膀胱产生的力量比野生型小鼠更少，对预处理的EFS和卡巴胆碱和阿托品后的EFS的反应，尽管差异不显著。令人惊讶的是，SMalphaA基因缺失小鼠的膀胱似乎功能正常，没有大体或组织学异常。结论：SMalphaA似乎是膀胱产生正常水平收缩力量所必需的。在这些动物的膀胱中没有观察到功能缺陷，但没有对这些膀胱施加压力。据我们所知，这项研究是第一次证明SMalphaA的表达在膀胱力产生中的重要性。
Purpose: Smooth muscle alpha-actin (SMalphaA) is an important actin isoform for functional contractility in the mouse bladder. Alterations in the expression of SMaA have been associated with a variety of bladder pathological conditions. Recently, a SMalphaA-null mouse was generated and differences in vascular tone and contractility were observed between wild-type and SMaA-null mice suggesting alterations in function of vascular smooth muscle. We used SMalphaA-null mice to explore the hypothesis that SMalphaA is necessary for normal bladder function.Materials and Methods: Reverse transcriptase polymerase chain reaction, Western blotting and immunohistochemical staining were used to confirm the absence of SMalphaA transcript and protein in the bladder of SMalphaA-null mice. In vitro bladder contractility compared between bladder rings harvested from wild-type and SMalphaA-null mice was determined by force measurement following electrical field stimulation (EFS), and exposure to chemical agonists and antagonists including KCl, carbachol, atropine and tetrodotoxin. Resulting force generation profiles for each tissue and agent were analyzed.Results: There was no detectable SMalphaA transcript and protein expression in the bladder of SMaA-null mice. Nine wild-type and 9 SMalphaA-null mice were used in the contractility study. Bladders from SMalphaA-null mice generated significantly less force than wild-type mice in response to EFS after KCl. Similarly, bladders from SMalphaA-null mice generated less force than wild-type mice in response to pretreatment EFS, and EFS after carbachol and atropine, although the difference was not significant. Surprisingly, the bladders in SMalphaA-null mice appeared to function normally and showed no gross or histological abnormalities.Conclusions: SMalphaA appears to be necessary for the bladder to be able to generate normal levels of contractile force. No functional deficits were observed in the bladders of these animals but no stress was placed on these bladders. To our knowledge this study represents the first report to demonstrate the importance of expression of SMalphaA in force generation in the bladder.