The protective effects of HGF against apoptosis in vascular endothelial cells caused by peripheral vascular injury

Abstract

Closed vascular injuries have danger of developing critical tissue ischemia with a high risk of amputation and limb loss. However, limited effective strategies exist at present. In this study, we investigate the role of hepatocyte growth factor (HGF) on apoptosis of vascular endothelial cells (VECs). First, apoptosis of VECs was induced by hypoxia treatment with or without HGF. Annexin V-7AAD apoptosis assay revealed that HGF overexpression significantly reduced VEC apoptosis. Then a closed peripheral vascular injury animal model was created by balloon catheter in female New Zealand rabbit. The VECs overexpressing HGF were injected into balloon injury rabbit. TUNEL and caspase 3 staining assays revealed that balloon catheter-treated artery showed severe intimal hyperplasia, with a 70% apoptosis rate (P < 0.05, vs. sham group), while HGF-overexpressing group showed a significant reduction of apoptosis. Furthermore, the expressions of Fas/FasL and their downstream apoptosis-related proteins were significantly decreased in HGF-overexpressing group when compared with those in balloon injury group as detected by western blot analysis. All these data indicated that HGF exhibited anti-apoptotic effects during VEC apoptosis, which might be mediated by the inhibition of Fas/FasL pathway. Our study provides a theoretic basis for the application of HGF in the gene therapy of closed peripheral vascular injury.

Hepatocyte growth factor (HGF) and stem cell factor (SCF) maintained the stemness of human bone marrow mesenchymal stem cells (hBMSCs) during long-term expansion by preserving mitochondrial function via the PI3K/AKT, ERK1/2, and STAT3 signaling pathways

“…We also confirmed that HGF and SCF increased the expression of mitochondrial-associated proteins, Catalase and SOD2, via activation of the PI3K/AKT and ERK1/2 signaling pathways, which have anti-apoptotic roles and regulate the apoptosis-related proteins, Bcl and Bax [48]. HGF and SCF modulated the osteogenic differentiation of MSCs through the ERK1/2 signaling pathway [49,50], effectively promoting the timely removal of excessive ROS in cells, reducing mitochondrial damage, and delaying cellular senescence.…”

Hepatocyte growth factor (HGF) and stem cell factor (SCF) maintained the stemness of human bone marrow mesenchymal stem cells (hBMSCs) during long-term expansion by preserving mitochondrial function via the PI3K/AKT, ERK1/2, and STAT3 signaling pathways

“…We also confirmed that HGF and SCF increased the expression of mitochondrial-associated proteins, Catalase and SOD2, via activation of the PI3K/AKT and ERK1/2 signaling pathways, which have antiapoptotic roles and regulate the apoptosis-related proteins, Bcl and Bax [38]. HGF and SCF modulated the osteogenic differentiation of MSCs through the ERK1/2 signaling pathway [39,40], effectively promoting the timely removal of excessive ROS in cells, reducing mitochondrial damage, and delaying cellular senescence.…”

Protective effects of hepatocyte growth factor gene overexpression against hydrogen peroxide‐induced apoptosis in mesenchymal stem cells

“…It has been reported that treatment with H 2 O 2 induced upregulation of proapoptotic proteins, such as Bax, cleaved caspase, and cleaved PARP and downregulation of the anti‐apoptotic proteins, such as Bcl‐2 in MSCs . However, overexpression of HGF downregulated proapoptotic proteins and upregulated antiapoptotic proteins induced by hypoxia in vascular endothelial cells . Additionally, H 2 O 2 ‐induced apoptosis was mitigated by HGF in human embryonic stem cell derived‐neural progenitors .…”

“…30 However, overexpression of HGF downregulated proapoptotic proteins and upregulated antiapoptotic proteins induced by hypoxia in vascular endothelial cells. 31 Additionally, H 2 O 2 -induced apoptosis was mitigated by HGF in human embryonic stem cell derived-neural progenitors. 32 Previous studies have reported that treatment with HGF prevented H 2 O 2 -induced apoptosis.…”