Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Biochem Biophys Res Commun ; 531(2): 133-139, 2020 10 15.
Article in English | MEDLINE | ID: mdl-32782147

ABSTRACT

Insulin-like growth factor binding protein 3 (IGFBP3) is a multifunctional protein, able either to stimulate the cell growth or to promote apoptosis. In particular, IGFBP3 plays significant role in propagation of stress-induced senescence in human endometrium-derived mesenchymal stem cells (MESCs) (Vassilieva et al., 2020). We undertook CRISPR/Cas9-mediated IGFBP3 knockout in an effort to decelerate stress-induced senescence in MESCs, but, unexpectedly, IGFBP3-knockout MESCs culture acquired chondrocyte-like features, such as cell condensation and aggregation. We revealed that IGFBP3-knockout MESCs completely lost CD73 and CD90 MESCs positive surface markers, and significantly decreased expression of CD105 and CD146 MESCs positive surface markers. In addition, we found IGFBP3-knockout MESCs aggregates positively stained for Alcian Blue. We also detected expression of collagen type II in IGFBP3-knockout MESCs. The obtained results indicate that MESCs lost stemness after IGFBP3-knockout and underwent differentiation toward chondrogenic lineage. Our findings can enlighten IGFBP3 role in regulation of MESCs chondrogenesis.


Subject(s)
Cell Differentiation , Chondrogenesis , Endometrium/cytology , Insulin-Like Growth Factor Binding Protein 3/deficiency , Mesenchymal Stem Cells/cytology , Biomarkers/metabolism , Female , Humans , Insulin-Like Growth Factor Binding Protein 3/metabolism , Multipotent Stem Cells/metabolism
2.
Aging (Albany NY) ; 12(2): 1987-2004, 2020 01 17.
Article in English | MEDLINE | ID: mdl-31951594

ABSTRACT

Stress-induced premature cell senescence is well recognized to be accompanied by emerging the senescence-associated secretory phenotype (SASP). Secreted SASP factors can promote the senescence of normal neighboring cells through autocrine/paracrine pathways and regulate the senescence response, as well. Regarding human endometrium-derived mesenchymal stem cells (MESCs), the SASP regulation mechanisms as well as paracrine activity of senescent cells have not been studied yet. Here, we examined the role of insulin-like growth factor binding protein 3 (IGFBP3) in the paracrine senescence induction in young MESCs. The H2O2-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.


Subject(s)
Endometrium/cytology , Endometrium/metabolism , Mesenchymal Stem Cells/metabolism , Paracrine Communication , Cellular Senescence , Endocytosis , Female , Humans , Hydrogen Peroxide/metabolism , Hydrogen Peroxide/pharmacology , Insulin-Like Growth Factor Binding Protein 3/genetics , Insulin-Like Growth Factor Binding Protein 3/metabolism , MAP Kinase Signaling System , Phosphatidylinositol 3-Kinases , Protein Transport , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction
SELECTION OF CITATIONS
SEARCH DETAIL
...