Effects of IGFBP3 knockdown on human endometrial mesenchymal stromal cells stress-induced senescence

Abstract

Insulin-like growth factor binding protein 3 (IGFBP3) is known for its pleiotropic ability to regulate various cellular processes such as proliferation, apoptosis, differentiation etc. It has recently been shown that IGFBP3 is part of the secretome of senescent human endometrial mesenchymal stromal cells (MESCs) (Griukova et al., 2019) that takes part in paracrine propagation of senescence-like phenotype in MESCs (Vassilieva et al., 2020); however, mechanisms of pro-senescent IGFBP3 action in MESCs remain still unexplored. This study is aimed at elucidating the role of IGFBP3 upregulation in senescent MESCs. IGFBP3 knockdown in MESCs committed to H2O2-induced senescence led to partial abrogation of p21/Rb axis, to elevated ERK phosphorylation and to increase in SA-β-gal activity. Additionally, MESCs derived from various donors were found to demonstrate different IGFBP3 regulation during stress-induced senescence. Obtained results suggest ambiguous role of IGFBP3 in stress-induced senescence of MESCs.