Capillary morphogenesis protein-2 is required for mouse parturition by maintaining uterine collagen homeostasis.
Capillary morphogenesis protein-2 is required for mouse parturition by maintaining uterine collagen homeostasis.
复制标题
DOI：
10.1016/j.bbrc.2012.04.160
复制
发表时间：
2012-06-08
影响因子：
3.1
通讯作者：
Liu S
中科院分区：
文献类型：
--
作者：
Peters DE;Zhang Y;Molinolo AA;Miller-Randolph S;Szabo R;Bugge TH;Leppla SH;Liu S
毛细血管形态发生蛋白 2 (CMG2) 作为炭疽毒素受体，在炭疽发病机制中发挥重要作用。尽管 CMG2 的突变已被确定会导致两种人类常染色体隐性遗传病，即青少年透明纤维瘤病和婴儿系统性透明质变病，这两种疾病的特征都是结缔组织中透明物质沉积过多，但 CMG2 的生理功能仍然难以捉摸。为了研究 CMG2 在正常生理学中的作用，我们对之前生成的 CMG2 缺失小鼠进行了详细的组织学分析。虽然在 CMG2−/− 雄性小鼠中没有观察到形态学或组织学缺陷，但 CMG2−/− 雌性小鼠由于分娩缺陷而无法产生任何后代。我们发现 CMG2 的缺失导致 CMG2−/− 雌性子宫肌层内胶原广泛沉积，导致子宫发生显着的形态变化。这种胶原蛋白的积累还导致 CMG2−/− 小鼠子宫肌层中平滑肌细胞的损失，显然使分娩过程中的子宫收缩功能丧失。结果，即使怀孕的 CMG2−/− 小鼠能够足月妊娠，但它们无法产下幼崽。然而，发育完全的胎儿可以通过剖腹产成功分娩，并在寄养时存活至成年。我们的结果表明，CMG2 不是正常小鼠胚胎发育所必需的，但对于小鼠分娩是必不可少的。与其在炭疽毒素结合和内化中的作用平行，本文中我们提供了证据表明 CMG2 可能充当胶原蛋白受体，这对于维持子宫内胶原蛋白稳态至关重要。
Capillary morphogenesis protein-2 (CMG2) functions as an anthrax toxin receptor that plays an essential role in anthrax pathogenesis. Although mutations in CMG2 have been identified to cause two human autosomal recessive disorders, Juvenile Hyaline Fibromatosis and Infantile Systemic Hyalinosis, both characterized by excess hyaline material deposition in connective tissues, the physiologic function of CMG2 remains elusive. To study the roles of CMG2 in normal physiology, here we performed detailed histological analyses of the CMG2-null mice we generated previously. While no morphological or histological defects were observed in CMG2−/− male mice, CMG2−/− female mice were unable to produce any offspring due to a defect in parturition. We found that deletion of CMG2 resulted in a diffuse deposition of collagen within the myometrium of CMG2−/− females, causing remarkable morphological changes to their uteri. This collagen accumulation also led to loss of smooth muscle cells in the myometrium of CMG2−/− mice, apparently disabling uterine contractile function during parturition. As a consequence, even though pregnant CMG2−/− mice were able to carry the gestation to full term, they were unable to deliver pups. However, the fully-developed fetuses could be successfully delivered by Cesarean section and survived to adulthood when fostered. Our results demonstrate that CMG2 is not required for normal mouse embryonic development but is indispensable for murine parturition. In parallel to its role in anthrax toxin binding and internalization, herein we provide evidence that CMG2 may function as a collagen receptor which is essential for maintaining collagen homeostasis in the uterus.
登录
查看更多内容
DOI：
10.1073/pnas.0431098100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Scobie, HM;Rainey, GJA;Young, JAT
通讯作者：
Young, JAT
影响因子：
30.3
作者：
Liu S;Miller-Randolph S;Crown D;Moayeri M;Sastalla I;Okugawa S;Leppla SH
通讯作者：
Leppla SH
影响因子：
64.8
作者：
Bradley, KA;Mogridge, J;Young, JAT
通讯作者：
Young, JAT
影响因子：
5.3
作者：
Wagenaar-Miller, Rebecca A.;Engelholm, Lars H.;Holmbeck, Kenn
通讯作者：
Holmbeck, Kenn
影响因子：
9.8
作者：
Dowling, O;Difeo, A;Martignetti, JA
通讯作者：
Martignetti, JA