Cervical Softening During Pregnancy: Regulated Changes in Collagen Cross-Linking and Composition of Matricellular Proteins in the Mouse
Cervical Softening During Pregnancy: Regulated Changes in Collagen Cross-Linking and Composition of Matricellular Proteins in the Mouse
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DOI：
10.1095/biolreprod.110.089599
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发表时间：
2011-05-01
影响因子：
3.6
通讯作者：
Mahendroo, Mala
中科院分区：
文献类型：
--
作者：
Akins, Meredith L.;Luby-Phelps, Katherine;Mahendroo, Mala
更好地了解分娩过程对于预防早产至关重要，美国每年出生的婴儿中有12.7%发生早产。宫颈重塑是这一过程的关键组成部分。从妊娠早期开始，重塑需要宫颈细胞外基质（ECM）的累积性、进行性变化，导致胶原纤维结构重组，拉伸强度逐渐丧失。在目前的研究中，我们进行了详细的生化分析的因素，在子宫颈，调节胶原蛋白结构在小鼠妊娠早期，包括蛋白质的表达参与处理的前胶原蛋白，组装的胶原纤维，交联形成，和沉积的胶原蛋白在ECM中。这些因素的变化与电子显微镜观察到的胶原交联类型和胶原纤维的堆积相关。在妊娠早期，血小板反应蛋白2和腱生蛋白C两种基质细胞蛋白的表达下降，赖氨酰羟化酶的表达也下降，赖氨酰羟化酶参与交联形成。这些变化伴随着妊娠第12天和第14天HP和LP交联分别下降，以及胶原纤维直径逐渐增加。相比之下，胶原蛋白的丰度在整个怀孕过程中保持不变。我们得出结论，宫颈软化过程中拉伸强度的早期变化部分来自胶原交联的数量和类型的变化，并与两种基质细胞蛋白血小板反应蛋白2和腱生蛋白C的表达下降有关。
A greater understanding of the parturition process is essential in the prevention of preterm birth, which occurs in 12.7% of infants born in the United States annually. Cervical remodeling is a critical component of this process. Beginning early in pregnancy, remodeling requires cumulative, progressive changes in the cervical extracellular matrix (ECM) that result in reorganization of collagen fibril structure with a gradual loss of tensile strength. In the current study, we undertook a detailed biochemical analysis of factors in the cervix that modulate collagen structure during early mouse pregnancy, including expression of proteins involved in processing of procollagen, assembly of collagen fibrils, cross-link formation, and deposition of collagen in the ECM. Changes in these factors correlated with changes in the types of collagen cross-links formed and packing of collagen fibrils as measured by electron microscopy. Early in pregnancy there is a decline in expression of two matricellular proteins, thrombospondin 2 and tenascin C, as well as a decline in expression of lysyl hydroxylase, which is involved in cross-link formation. These changes are accompanied by a decline in both HP and LP cross-links by gestation Days 12 and 14, respectively, as well as a progressive increase in collagen fibril diameter. In contrast, collagen abundance remains constant over the course of pregnancy. We conclude that early changes in tensile strength during cervical softening result in part from changes in the number and type of collagen cross-links and are associated with a decline in expression of two matricellular proteins thrombospondin 2 and tenascin C.