Manase Kengo, Endo Toshiaki, Chida Mitunobu, Nagasawa Kunihiko, Honnma Hiroyuki, Yamazaki Kiyohiro, Kitajima Yoshimitu, Goto Taeko, Kanaya Mika, Hayashi Takuhiro, Mitaka Toshihiro, Saito Tsuyoshi
Department of Obstetrics and Gynecology, Sapporo Medical University School of Medicine, South-1 West-16, Chuou-ku, Sapporo 060-8543, Japan.
Reprod Biol Endocrinol. 2006 Jun 2;4:32. doi: 10.1186/1477-7827-4-32.
The changes occurring in the rodent uterus after parturition can be used as a model of extensive tissue remodeling. As the uterus returns to its prepregnancy state, the involuting uterus undergoes a rapid reduction in size primarily due to the degradation of the extracellular matrix, particularly collagen. Membrane type-I matrix metalloproteinase (MT1-MMP) is one of the major proteinases that degrades collagen and is the most abundant MMP form in the uterus. Matrix metalloproteinase-2(MMP-2) can degrade type I collagen, although its main function is to degrade type IV collagen found in the basement membrane. To understand the expression patterns of matrix metalloproteinases (MMPs) in the rat uterus, we analyzed their activities in postpartum uterine involution.
We performed gelatin zymography, northern blot analysis and immunohistochemistry to compare the expression levels of MT1-MMP, MMP-2, matrix metalloproteinase-9 (MMP-9) and the tissue inhibitors of MMPs-1 and 2 (TIMP-1 and TIMP-2) in the rat uterus 18 h, 36 h and 5 days after parturition with their expression levels during pregnancy (day 20).
We found that both MT1-MMP and MMP-2 localized mainly in the cytoplasm of uterine interstitial cells. The expression levels of MT1-MMP and MMP-2 mRNAs and the catalytic activities of the expressed proteins significantly increased 18 h and 36 h after parturition, but at postpartum day 5, their mRNA expression levels and catalytic activities decreased markedly. The expression levels of MMP-9 increased 18 h and 36 h after parturition as determined by gelatin zymography including the expression levels of TIMP-1 and TIMP-2.
These expression patterns indicate that MT1-MMP, MMP-2, MMP-9, TIMP-1 and TIMP-2 may play key roles in uterine postpartum involution and subsequent functional regenerative processes.
分娩后啮齿动物子宫发生的变化可作为广泛组织重塑的模型。随着子宫恢复到妊娠前状态， involuting子宫的大小迅速减小，这主要是由于细胞外基质尤其是胶原蛋白的降解。膜型-I基质金属蛋白酶（MT1-MMP）是降解胶原蛋白的主要蛋白酶之一，也是子宫中最丰富的MMP形式。基质金属蛋白酶-2（MMP-2）可以降解I型胶原蛋白，尽管其主要功能是降解基底膜中发现的IV型胶原蛋白。为了了解基质金属蛋白酶（MMPs）在大鼠子宫中的表达模式，我们分析了它们在产后子宫复旧中的活性。
我们进行了明胶酶谱分析、Northern印迹分析和免疫组织化学，以比较产后18小时、36小时和5天大鼠子宫中MT1-MMP、MMP-2、基质金属蛋白酶-9（MMP-9）以及MMPs-1和2的组织抑制剂（TIMP-1和TIMP-2）的表达水平与妊娠期间（第20天）的表达水平。
我们发现MT1-MMP和MMP-2主要定位于子宫间质细胞的细胞质中。MT1-MMP和MMP-2 mRNA的表达水平以及所表达蛋白质的催化活性在产后18小时和36小时显著增加，但在产后第5天，它们的mRNA表达水平和催化活性明显下降。通过明胶酶谱分析确定，包括TIMP-1和TIMP-2的表达水平在内，MMP-9的表达水平在产后18小时和36小时增加。
这些表达模式表明，MT1-MMP、MMP-2、MMP-9、TIMP-1和TIMP-2可能在子宫产后复旧及随后的功能再生过程中起关键作用。
