Laviola Luigi, Perrini Sebastio, Belsanti Gaetana, Natalicchio Annalisa, Montrone Carmela, Leonardini Anna, Vimercati Antonella, Scioscia Marco, Selvaggi Luigi, Giorgino Riccardo, Greco Pantaleo, Giorgino Francesco
Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology and Metabolic Diseases, University of Bari, Piazza Giulio Cesare 11, I-70124 Bari, Italy.
Endocrinology. 2005 Mar;146(3):1498-505. doi: 10.1210/en.2004-1332. Epub 2004 Nov 24.
The IGFs promote the growth and development of the feto-placental unit during gestation, and impairment of their placental actions may result in altered intrauterine growth of the fetus. In this study, proteins involved in IGF signaling were investigated in human placentas from pregnancies complicated by intrauterine growth restriction (IUGR) compared with those from normal pregnancies. IUGR placentas exhibited 33% reduction in the protein content of IGF-I receptors, but no changes in insulin receptor protein levels. In addition, insulin receptor substrate-2 (IRS-2) protein levels were reduced in IUGR placentas, with no changes in IRS-1 or Shc protein content, and this was associated with a parallel decrease in IRS-2-associated phosphatidyl inositol 3-kinase. Akt protein expression was also reduced in IUGR, whereas phosphorylation of Akt and its substrate glycogen synthase kinase-3 was unchanged. Finally, in IUGR placentas there was impaired activation of multiple members of the MAPK family, because phosphorylation of p38 and c-Jun N-terminal kinase was reduced 70%. In conclusion, human placentas from pregnancies complicated by IUGR are characterized by decreased IGF-I receptor content, selective impairment of the IRS-2/ phosphatidyl inositol 3-kinase pathway, and reduced p38 and c-Jun N-terminal kinase activation. The observed abnormalities in IGF-I signaling may contribute to altered fetal growth and development in human IUGR.
胰岛素样生长因子（IGFs）在妊娠期促进胎儿 - 胎盘单位的生长和发育，其胎盘作用受损可能导致胎儿宫内生长改变。在本研究中，将合并宫内生长受限（IUGR）妊娠的人胎盘与正常妊娠的人胎盘相比，对参与IGF信号传导的蛋白质进行了研究。IUGR胎盘的IGF - I受体蛋白含量降低了33%，但胰岛素受体蛋白水平无变化。此外，IUGR胎盘的胰岛素受体底物 - 2（IRS - 2）蛋白水平降低，IRS - 1或Shc蛋白含量无变化，且这与IRS - 2相关的磷脂酰肌醇3 - 激酶平行降低有关。IUGR中Akt蛋白表达也降低，而Akt及其底物糖原合酶激酶 - 3的磷酸化未改变。最后，在IUGR胎盘中，丝裂原活化蛋白激酶（MAPK）家族多个成员的激活受损，因为p38和c - Jun氨基末端激酶的磷酸化降低了70%。总之，合并IUGR妊娠的人胎盘的特征是IGF - I受体含量降低、IRS - 2/磷脂酰肌醇3 - 激酶途径的选择性受损以及p38和c - Jun氨基末端激酶激活减少。在IGF - I信号传导中观察到的异常可能导致人类IUGR中胎儿生长和发育改变。
