Lei H, Kalluri R, Furth E E, Baker A H, Strauss J F
Center for Research on Reproduction and Women's Health and Department of Obstetrics and Gynecology, University of Pennsylvania Medical Center, Philadelphia 19104, USA.
Biol Reprod. 1999 Jan;60(1):176-82. doi: 10.1095/biolreprod60.1.176.
We report here that rat amnion type IV collagens are composed primarily of alpha1(IV) and alpha2(IV) chains. Amnion basement membrane collagens were more sensitive to degradation by collagenases than were adult rat kidney basement membrane collagens, which are enriched in alpha3(IV), alpha4(IV), and alpha6(IV) chains. Amnion type IV collagen content per unit of protein was markedly reduced by Day 21 of pregnancy, the day of delivery. Increased amnion levels of matrix metalloproteinase (MMP)-2 and MMP-9, gelatinases that degrade type IV collagen, were found by Day 21, suggesting that collagen breakdown was responsible, in part, for the decline in amnion type IV collagen. Infection of organ cultures of Day 18 rat amnions with a recombinant adenovirus expressing MMP-9 (AdMMP-9) caused release of collagen fragments detected as hydroxyproline in the culture fluid, amnion cell detachment, and apoptosis. The AdMMP-9-induced apoptosis was prevented by the MMP inhibitor batimastat. These findings suggest that MMPs are implicated in anoikis and apoptotic death of amnion cells, and may be part of a complex program of fetal membrane remodeling that occurs before delivery.
我们在此报告，大鼠羊膜IV型胶原主要由α1(IV)和α2(IV)链组成。羊膜基底膜胶原比成年大鼠肾脏基底膜胶原对胶原酶降解更敏感，成年大鼠肾脏基底膜胶原富含α3(IV)、α4(IV)和α6(IV)链。妊娠第21天（分娩日）时，每单位蛋白质的羊膜IV型胶原含量显著降低。到第21天时，发现羊膜中基质金属蛋白酶（MMP）-2和MMP-9（可降解IV型胶原的明胶酶）水平升高，这表明胶原分解在一定程度上导致了羊膜IV型胶原的减少。用表达MMP-9的重组腺病毒（AdMMP-9）感染第18天大鼠羊膜的器官培养物，导致培养液中以羟脯氨酸形式检测到胶原片段的释放、羊膜细胞脱离和凋亡。MMP抑制剂batimastat可阻止AdMMP-9诱导的凋亡。这些发现表明，MMPs与羊膜细胞的失巢凋亡和凋亡性死亡有关，可能是分娩前胎膜重塑复杂程序的一部分。
