Myoepithelial Cell Contraction and Milk Ejection Are Impaired in Mammary Glands of Mice Lacking Smooth Muscle Alpha-Actin
Myoepithelial Cell Contraction and Milk Ejection Are Impaired in Mammary Glands of Mice Lacking Smooth Muscle Alpha-Actin
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DOI：
10.1095/biolreprod.110.090639
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发表时间：
2011-07-01
影响因子：
3.6
通讯作者：
Tomasek, James J.
中科院分区：
文献类型：
--
作者：
Haaksma, Carol J.;Schwartz, Robert J.;Tomasek, James J.
乳腺肌上皮细胞是特化的平滑肌样上皮细胞，表达平滑肌肌动蛋白亚型：平滑肌α-肌动蛋白（ACTA2）。这些细胞响应催产素而收缩，产生哺乳期间排乳所需的收缩力。据信 ACTA2 有助于肌上皮收缩力的产生；然而，这一假设尚未得到直接检验。为了评估 ACTA2 对乳腺肌上皮细胞收缩的贡献，使用 Acta2 缺失小鼠并评估乳汁排出和肌上皮细胞收缩力的产生。在Acta2无效母鼠上哺乳的幼崽在出生后立即开始体重增加显着减少。交叉寄养证明 Acta2 无效母鼠存在泌乳缺陷。胭脂红明矾整体封片和常规组织学显示，Acta2 无效乳腺中没有潜在的结构缺陷，可以解释泌乳缺陷。此外，使用 Acta2 启动子-GFP 转基因或鬼笔环肽染色来观察肌上皮细胞进行评估，在 Acta2 缺失的哺乳期乳腺中，肌上皮细胞形成和组织看起来正常。然而，在分离的 Acta2 缺失的哺乳期乳腺中以及使用 Acta2 缺失的哺乳母鼠的体内研究中，催产素响应的乳腺肌上皮细胞收缩显着减少。这些结果表明，缺乏ACTA2表达会损害乳腺肌上皮细胞收缩和乳汁排出，并表明乳腺肌上皮细胞中ACTA2表达具有增强乳汁排出所需的收缩力产生的功能结果。
Mammary myoepithelial cells are specialized smooth muscle-like epithelial cells that express the smooth muscle actin isoform: smooth muscle alpha-actin (ACTA2). These cells contract in response to oxytocin to generate the contractile force required for milk ejection during lactation. It is believed that ACTA2 contributes to myoepithelial contractile force generation; however, this hypothesis has not been directly tested. To evaluate the contribution of ACTA2 to mammary myoepithelial cell contraction, Acta2 null mice were utilized and milk ejection and myoepithelial cell contractile force generation were evaluated. Pups suckling on Acta2 null dams had a significant reduction in weight gain starting immediately postbirth. Cross-fostering demonstrated the lactation defect is with the Acta2 null dams. Carmine alum whole mounts and conventional histology revealed no underlying structural defects in Acta2 null mammary glands that could account for the lactation defect. In addition, myoepithelial cell formation and organization appeared normal in Acta2 null lactating mammary glands as evaluated using an Acta2 promoter-GFP transgene or phalloidin staining to visualize myoepithelial cells. However, mammary myoepithelial cell contraction in response to oxytocin was significantly reduced in isolated Acta2 null lactating mammary glands and in in vivo studies using Acta2 null lactating dams. These results demonstrate that lack of ACTA2 expression impairs mammary myoepithelial cell contraction and milk ejection and suggests that ACTA2 expression in mammary myoepithelial cells has the functional consequence of enhancing contractile force generation required for milk ejection.