Article Text

GW24-e2328 Angiopoietin-Like 4 protects mesenchymal stem cells against hypoxia and serum deprivation-induced apoptosis
  1. Hou Meng,
  2. Wang Yong Shun,
  3. Yu Bo
  1. Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University


Objectives To test the hypothesis that Angiopoientin-Like4 (ANGPTL4) protects rat bone marrow-derived mesenchymal stem cells (BM-MSCs) from apoptosis induced by hypoxia/serum deprivation (hypoxia/SD) through integrin induced PI3K/Akt signalling pathway

Methods BM-MSCs were cultured in hypoxia/SD environment to induce apoptosis. The rate of apoptosis was tested by FACS, and the expression of integrin was examined by rtPCR, while the PI3K/Akt and ERK1/2 signalling pathway were tested by western blot analysis.

Results ANGPTL4 protected BM-MSCs from apoptosis, showing that the apoptotic index decreased 4 to 5 folds relative to control. While the expression of integrin was increased 2 to 3 folds, and the integrin associated PI3K/Akt and ERK1/2 signalling pathway were activated, showing that the ratio of phosphorylated Akt (S473), Akt (T308)/dephosphorylated Akt were increased 3 to 4 folds relative to control, and the phosphorylated ERK1/2(T203/Y204)/dephosphorylated ERK1/2 2 to 3 folds relative to control.

Conclusions Autologous MSCs offer a great advantage when used to regenerate and repopulate the injured myocardium, restoring its function after transplantation into ischaemic or infarcted heart. However, the ratio of MSC engraftment is extremely low due to a low rate of cell survival, induced by the ischaemic environment into which they are introduced in vivo. Indeed, engrafted MSCs first encounter harsh conditions coupled with the loss of survival signals because of an inadequate interaction between cells and matrix. Recent studies has confirmed that in tumor cells, ANGPTL4 secreted by tumor cells contacting with the integrins helped the tumor cells escape from apoptosis caused by losing integrin-mediated ECM contact, mimicking the survival signals even in the absence of ECM and cell-cell contact. So here we suppose that ANGPTL4 may take the same effect on the MSCs. Experiments were therefore carried out to examine the antiapoptotic actions of ANGPTL4 on MSCs. Our findings demonstrated that ANGPTL4-mediated integrin engagement activating focal adhesion kinases, such as FAK and Src, which leads to PI3K/Akt, ERK1/2 prosurvival signals and sustains anchorage-related signals even in the absence of ECM and cell-cell contact. Our findings raise a new way to protect MSCs from apoptosis and are of considerable therapeutic significance and provide the potential of now exploiting ANGPTL4 and MSCs clinically in cardiac regeneration.

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