Paracrine senescence of human endometrial mesenchymal stem cells: a role for the insulin-like growth factor binding protein 3
Irina O. Vassilieva, Vera Kosheverova, Mikhail A. Vitte, Rimma Kamentseva, Alla Shatrova, Н. В. Цупкина, Elena V. Skvortsova, Aleksandra V. Borodkina, Elena Tolkunova, Nikolay Nikolsky, Elena Burova
Abstract
-induced premature senescence of MESCs led to increased IGFBP3 in conditioned media (CM). The inhibitory analysis of both MAPK and PI3K signaling pathways showed that IGFBP3 releasing from senescent cells is mainly regulated by PI3K/Akt pathway activity. IGFBP3 appears to be an important senescence-mediating factor as its immunodepletion from the senescent CM weakened the pro-senescent effect of CM on young MESCs and promoted their growth. In contrast, young MESCs acquired the senescence phenotype in response to simultaneous addition of recombinant IGFBP3 (rIGFBP3). The mechanism of extracellular IGFBP3 internalization was also revealed. The present study is the first to demonstrate a significant role of extracellular IGFBP3 in paracrine senescence induction of young MESCs.