Morimoto T, Head J R, MacDonald P C, Casey M L
The Cecil H. and Ida Green Center for Reproductive Biology Sciences and the Departments of Obstetrics-Gynecology, Biochemistry, and Cell Biology-Neuroscience, The University of Texas Southwestern Medical School, Dallas, Texas 75235-9051, USA.
Biol Reprod. 1998 Oct;59(4):862-70. doi: 10.1095/biolreprod59.4.862.
The activation of latent transforming growth factor beta (L-TGFbeta) is essential for the action of TGFbeta, which, in turn, is involved in the regulation of expression of some progesterone-responsive genes. One mechanism by which TGFbeta is activated involves thrombospondin (TSP), a protein that binds extracellular proteins. Immunoreactive TSP (irTSP) protein and TSP-1 mRNA in myometrial tissues of ovulatory and pregnant women were localized by immunohistochemistry and in situ hybridization. IrTSP and TSP-1 mRNA were randomly distributed in myometrial smooth muscle cells of some, but not all, tissues of pregnant women at term before labor; but in some areas of most of these tissues, irTSP was intense and commonly localized extracellularly. Intense irTSP and TSP-1 mRNA in myocytes were more common in myometrium during labor. In myometrium from ovulatory women (n = 26), irTSP was localized primarily in vascular smooth muscle cells and was detected occasionally in scattered myocytes. Little TSP-1 mRNA was demonstrable by in situ hybridization in vessels or myocytes of myometrial tissue from ovulatory women (n = 7). By Northern analysis of total RNA, TSP-1 mRNA was detected in myometrial tissue of pregnant women and in human myometrial smooth muscle cells in culture. The levels of TSP-1 mRNA in myometrial tissues of pregnant women during labor (n = 18) were greater than those in myometrium at > 37 wk gestation before labor began (n = 25, p < 0.001). The ratios of TSP-1 to glyceraldehyde 3-phosphate dehydrogenase mRNAs in 3 myometrial tissues during oxytocin-induced labor were not statistically different from those in myometrium during spontaneous labor but were greater than those in myometrium before labor (p < 0.05). The level of TSP-1 mRNA in confluent human myometrial cells in culture was relatively high, was increased by treatment with fetal bovine serum, and was decreased by treatment with platelet-derived growth factor or activators of adenylyl cyclase or protein kinase C. Myometrial cells in culture constitute a useful model for studying the regulation of TSP-1 gene expression in human myometrium.
潜伏转化生长因子β（L-TGFβ）的激活对于TGFβ的作用至关重要，而TGFβ又参与某些孕激素反应性基因表达的调控。TGFβ激活的一种机制涉及血小板反应蛋白（TSP），它是一种能结合细胞外蛋白的蛋白质。通过免疫组织化学和原位杂交对排卵妇女和孕妇子宫肌层组织中的免疫反应性TSP（irTSP）蛋白和TSP-1 mRNA进行定位。在足月临产前孕妇部分（而非全部）子宫肌层组织的平滑肌细胞中，irTSP和TSP-1 mRNA呈随机分布；但在这些组织大多数的某些区域，irTSP强烈且通常定位于细胞外。分娩时子宫肌层中肌细胞内强烈的irTSP和TSP-1 mRNA更为常见。在排卵妇女的子宫肌层（n = 26）中，irTSP主要定位于血管平滑肌细胞，偶尔在散在的肌细胞中检测到。在排卵妇女子宫肌层组织（n = 7）的血管或肌细胞中，原位杂交几乎未检测到TSP-1 mRNA。通过对总RNA进行Northern分析，在孕妇子宫肌层组织和培养的人子宫肌层平滑肌细胞中检测到TSP-1 mRNA。分娩时孕妇子宫肌层组织（n = 18）中TSP-1 mRNA的水平高于临产前妊娠> 37周时子宫肌层的水平（n = 25，p < 0.001）。在催产素诱导分娩期间，3个子宫肌层组织中TSP-1与甘油醛-3-磷酸脱氢酶mRNA的比值与自然分娩时子宫肌层中的比值无统计学差异，但高于分娩前子宫肌层中的比值（p < 0.05）。培养的汇合人子宫肌层细胞中TSP-1 mRNA水平相对较高，用胎牛血清处理后升高，用血小板衍生生长因子或腺苷酸环化酶或蛋白激酶C激活剂处理后降低。培养的子宫肌层细胞是研究人子宫肌层中TSP-1基因表达调控的有用模型。
