Capillary morphogenesis protein-2 is required for mouse parturition by maintaining uterine collagen homeostasis

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• 作者：Diane E. Peters^a ; ^c ; Yi Zhang^b ; Alfredo A. Molinolo^a ; Sharmina Miller-Randolph^b ; Roman Szabo^a ; Thomas H. Bugge^a ; Stephen H. Leppla^b ; Shihui Liu^b ; ^{shliu@niaid.nih.gov}
• 关键词：CMG2 ; capillary morphogenesis protein-2 ; TEM8 ; tumor endothelium marker-8 ; ISH ; Infantile Systemic Hyalinosis ; JHF ; Juvenile Hyaline Fibromatosis
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：8 June, 2012
• 卷：422
• 期：3
• 页码：393-397
• 文件大小：1111 K

摘要

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^{鈭?鈭?/sup>} male mice, CMG2^{鈭?鈭?/sup>} 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^{鈭?鈭?/sup>} females, causing remarkable morphological changes to their uteri. This collagen accumulation also led to loss of smooth muscle cells in the myometrium of CMG2^{鈭?鈭?/sup>} mice, apparently disabling uterine contractile function during parturition. As a consequence, even though pregnant CMG2^{鈭?鈭?/sup>} 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.