Pelvic organ prolapse in fibulin-5 knockout mice - Pregnancy-induced changes in elastic fiber homeostasis in mouse vagina
Pelvic organ prolapse in fibulin-5 knockout mice - Pregnancy-induced changes in elastic fiber homeostasis in mouse vagina
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DOI：
10.2353/ajpath.2007.060662
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发表时间：
2007-02-01
影响因子：
6
通讯作者：
Word, R. Ann
中科院分区：
文献类型：
--
作者：
Drewes, Peter G.;Yanagisawa, Hiromi;Word, R. Ann
盆腔器官脱垂与阴道分娩史密切相关。然而，妊娠和分娩导致盆腔器官支持结构失效的机制尚不清楚。最近，有报道称赖氨酰氧化酶样1（LOXL1）基因缺失突变的小鼠会发生盆腔器官脱垂。弹性蛋白是赖氨酰氧化酶（LOX）和LOXL1的底物，且LOXL1与 fibulin - 5（FBLN5）相互作用。因此，为阐明弹性纤维组装在盆腔器官脱垂发病机制中的潜在作用，对Fbln5（-/-）小鼠的盆腔器官支持结构进行了研究，并测定了妊娠和分娩期间小鼠阴道内弹性纤维稳态的变化。Fbln5（-/-）小鼠的盆腔器官脱垂与灵长类动物的情况非常相似。阴道中LOX mRNA和蛋白质、LOXL1蛋白质的加工、FBLN5和原弹性蛋白以及锁链素含量之间的时间关系表明，产后阴道壁会发生弹性纤维组装和交联的爆发。结合Fbln5（-/-）小鼠的表型，结果表明弹性纤维的合成和组装对于阴道分娩后盆腔器官支持结构的恢复至关重要，并且弹性纤维稳态失调是小鼠盆腔器官脱垂发病机制中的一个主要事件。
Pelvic organ prolapse is strongly associated with a history of vaginal delivery. The mechanisms by which pregnancy and parturition lead to failure of pelvic organ support, however, are not known. Recently, it was reported that mice with null mutations in lysyl oxidase-like 1 (LOXL1) develop pelvic organ prolapse. Elastin is a substrate for lysyl oxidase (LOX) and LOXL1, and LOXL1 interacts with fibulin-5 (FBLN5). Therefore, to clarify the potential role of elastic fiber assembly in the pathogenesis of pelvic organ prolapse, pelvic organ support was characterized in Fbln5(-/-) mice, and changes in elastic fiber homeostasis in the mouse vagina during pregnancy and parturition were determined. Pelvic organ prolapse in Fbln5(-/-) mice was remarkably similar to that in primates. The temporal relationship between LOX mRNA and protein, processing of LOXL1 protein, FBLN5 and tropoelastin protein, and desmosine content in the vagina suggest that a burst of elastic fiber assembly and cross linking occurs in the vaginal wall postpartum. Together with the phenotype of Fbln5(-/-) mice, the results suggest that synthesis and assembly of elastic fibers are crucial for recovery of pelvic organ support after vaginal delivery and that disordered elastic fiber homeostasis is a primary event in the pathogenesis of pelvic organ prolapse in mice.