Torday J S, Kourembanas S
Joint Program in Neonatology, Brigham Women's Hospital, Boston, Massachusetts 02115.
Dev Biol. 1990 May;139(1):35-41. doi: 10.1016/0012-1606(90)90276-o.
Normal growth and differentiation of the lung depends upon mesenchymal-epithelial interactions during development. Recombination experiments using immature (Day 17) and mature (Day 21) fetal rat lung fibroblasts (FRLF) revealed that the stimulatory effect of mature fibroblasts on fetal type II epithelial cells is blocked by immature fibroblasts. Similarly, conditioned medium from Day 17 FRLFs blocks the stimulatory effect (fibroblast-pneumonocyte factor) of Day 21 conditioned medium on type II epithelial cells. This blocking activity is nondialyzable, trypsin sensitive, and heat stable. Its activity is neutralized by an antibody to TGF beta, in both conditioned media and recombined cell studies, and its activity is mimicked by TGF beta. Developmentally, TGF beta-like activity is present in conditioned medium from 15- to 19-day FRLF, decreasing precipitously between 19 and 21 days gestation. Northern blot analysis of mRNAs from fetal rat lung fibroblasts on Days 17, 19, and 21 revealed expression of TGF beta at all three stages of development.
肺的正常生长和分化取决于发育过程中的间充质-上皮相互作用。使用未成熟(第17天)和成熟(第21天)胎鼠肺成纤维细胞(FRLF)进行的重组实验表明,未成熟的成纤维细胞会阻断成熟成纤维细胞对胎儿II型上皮细胞的刺激作用。同样,来自第17天FRLF的条件培养基会阻断第21天条件培养基对II型上皮细胞的刺激作用(成纤维细胞-肺细胞因子)。这种阻断活性不能透析,对胰蛋白酶敏感,且热稳定。在条件培养基和重组细胞研究中,其活性均被抗TGF-β抗体中和,并且其活性可被TGF-β模拟。在发育过程中,15至19天的FRLF条件培养基中存在TGF-β样活性,在妊娠19至21天之间急剧下降。对第17、19和21天胎鼠肺成纤维细胞的mRNA进行Northern印迹分析,结果显示在发育的所有三个阶段均有TGF-β表达。