Abstract 3619: GATA-4 Increases Mesenchymal Stem Cell Survival in Ischemic Environment via Activating HO-1
Our previous studies indicate that GATA-4 plays an important role in ischemic heart repair mediated by mesenchymal stem cells (MSC). However, the underlying mechanism remains to be unknown. Heme oxygenase-1 (HO-1) is a stress-inducible rate-limiting protein which regulates heme degradation and takes part in cytoprotective activity under ischemic environment. We hypothesized that GATA-4 enhanced MSC mediated heart repair via promoting MSC survival and activating HO-1.
Methods: GATA-4 was transfected to MSC (MSCGATA-4) using pMSCV retroviral expression system. MSC transfected with GFP (MSCGFP) was used as control. The expression of HO-1 was assayed in MSC by microarray and Western Blot. MSC (2×106/50μl) were transplanted into the border area of ischemic rat hearts which underwent left anterior descending coronary artery ligation. MSC survival was evaluated by estimating the expression of Sry gene in female ischemic myocardium and by measuring MTT uptake by MSC following exposure to hypoxia in vitro.
Results: Cardiac function was significantly improved in animals which transplanted with MSCGATA-4 (Fig. A⇓). Survival of MSCGATA-4 in ischemic heart was significantly increased (Fig. B⇓). HO-1 was markedly overexpressed in MSCGATA-4, both at RNA (3.52±0.30 fold vs MSCGFP) and protein levels (Fig. C⇓). The MTT uptake was significantly higher in MSCGATA-4 than that in MSCGFP after cells were exposed to hypoxia for 48 and 72 hours. However, the effects of GATA-4 were partially abolished by HO-1 inhibitor—ZnPPIX, in a concentration dependent manner (Fig. D⇓).
Conclusions: These results suggest that GATA-4 promotes MSC survival through activation of HO-1.