Role of lysyl oxidase like 1 in regulation of postpartum connective tissue metabolism in the mouse vagina
Role of lysyl oxidase like 1 in regulation of postpartum connective tissue metabolism in the mouse vagina
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DOI：
10.1093/biolre/ioz148
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发表时间：
2019-11-01
影响因子：
3.6
通讯作者：
Damaser, Margot S.
中科院分区：
文献类型：
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作者：
Borazjani, Ali;Couri, Bruna M.;Damaser, Margot S.
赖氨酰氧化酶样 1 敲除 (Loxl1 KO) 小鼠的盆腔器官脱垂 (POP) 主要发生在经产小鼠中，在未产小鼠中罕见。我们确定了 Loxl1 缺乏对妊娠 20 天或产后 4 小时、48 小时、7 天、15 天、25 天、7 周或 12 周时阴道内结缔组织代谢基因和降解酶活性的产后调节的影响。未产的 Loxl1 KO 小鼠和 11、18 或 23 周龄的野生型 (WT) 小鼠作为对照。分别使用实时定量逆转录PCR和荧光素缀合明胶酶谱法评估基因表达和酶活性。产次对产后时间以及 KO 和 WT 小鼠之间的基因表达有显着影响，但对衰老没有影响。 Mmp2、Timp1、Timp2、Timp3、Timp4、Col1a1、Col3a1、Acta2 和 Bmp1 在 KO 和 WT 小鼠之间差异表达。基因-基因对的相关分析显示，经产 KO 和 WT 组之间有 10 个显着差异，其中 5 个是由于 KO 小鼠中缺乏 Bmp1 共表达。与 KO 小鼠相比，产后 25 天和 12 周，可归因于 MMP 的总体酶活性在 WT 中显着较高，并且在产后 15 天和 25 天，与 KO 未产对照小鼠相比，MMP 活性显着降低，但 WT 则不然。这些发现表明 Loxl1 缺乏与胎次相结合对产后结缔组织代谢的调节具有显着影响，特别是因为它与 Bmp1 的共表达和蛋白水解活性的改变有关。
Pelvic organ prolapse (POP) in lysyl oxidase like-1 knockout (Loxl1 KO) mice occurs primarily in parous mice and is rare in nulliparous mice. We determined the effect of Loxl1 deficiency on postpartum regulation of connective tissue metabolism genes and degradative enzyme activity in the vagina at 20 days gestation or 4 h, 48 h, 7 days, 15 days, 25 days, 7 weeks, or 12 weeks postpartum. Nulliparous Loxl1 KO and wildtype (WT) mice aged 11, 18, or 23 weeks were controls. Gene expression and enzyme activity were assessed using real-time quantitative reverse transcription PCR and fluorescein conjugated gelatin zymography, respectively. Parity, but not aging, had a significant influence on gene expression both with time postpartum and between KO and WT mice. Mmp2, Timp1, Timp2, Timp3, Timp4, Col1a1, Col3a1, Acta2, and Bmp1 were differentially expressed between KO and WT mice. Correlational analysis of gene-gene pairs revealed 10 significant differences between parous KO and WT groups, 5 of which were due to lack of co-expression of Bmp1 in KO mice. The overall enzyme activity that could be attributed to MMPs was significantly higher in WT compared to KO mice both 25 days and 12 weeks postpartum, and MMP activity was significantly lower 15 days and 25 days postpartum compared to KO nulliparous controls, but not WT. These findings suggest that Loxl1 deficiency combined with parity has a significant impact on postpartum regulation of connective tissue metabolism, particularly as it relates to co-expression of Bmp1 and altered proteolytic activity.