Disruption of the TIMP-1 gene product is associated with accelerated endometrial gland formation during early postnatal uterine development.
Disruption of the TIMP-1 gene product is associated with accelerated endometrial gland formation during early postnatal uterine development.
复制标题
TIMP-1 基因产物的破坏与产后子宫发育早期子宫内膜腺体形成的加速有关。
DOI：
10.1095/biolreprod.104.029181
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Nothnick,WarrenB
中科院分区：
文献类型：
--
作者：
Zhou,Han-E;Zhang,Xuan;Nothnick,WarrenB
Postnatal uterine development is marked by periods of tissue remodeling. The objective of the present study was to examine the role of tissue inhibitor of metalloproteinase-1 (TIMP-1), a regulator of tissue remodeling events, during postnatal uterine development and to assess the phenotypic consequences of disruption of theTIMP-1gene product during this time period. To accomplish this goal, wild-type andTIMP-1null mice were sacrificed at Postnatal Days (PNDs) 5, 10, 15, 20, and 25 and uterine morphology,TIMPexpression and matrix metalloproteinase (MMP) activity were assessed. In wild-type mice,TIMP-1mRNA steady-state levels were highest at PND 5, after which expression decreased.TIMP-2andTIMP-3expression in wild-type mice showed no significant changes from PND 5 to 25. InTIMP-1null mice,TIMP-2andTIMP-3expression patterns were similar to those in wild-type counterparts with the exception that, at PND 10,TIMP-2andTIMP-3expression was significantly lower in the null mice. Endometrial gland number and uterine histology were similar between genotypes at PNDs 5 and 10, but at PNDs 15 and 20, endometrial glands were more abundant inTIMP-1null mice. Associated with the increased gland density in the null mice was an increase in total MMP activity above the levels expressed in wild-type mice. In summary, disruption of theTIMP-1gene product is associated with reducedTIMP-2andTIMP-3steady-state mRNA levels, elevated MMP activity, and accelerated endometrial gland formation. We conclude that, during early postnatal uterine development, TIMP-1 may be critical for proper endometrial gland development.
