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. 2019 Jun 29:25:4811-4818.
doi: 10.12659/MSM.914035.

Role of Programmed Cell Death 4 (PDCD4)-Mediated Akt Signaling Pathway in Vascular Endothelial Cell Injury Caused by Lower-Extremity Ischemia-Reperfusion in Rats

Huanhuan Chen  1 , Haifeng Zhu  2 , Jin Yang  1 , Yuefeng Zhu  1 , Jinhua Mei  1 , Haigang Shen  1 , Kai Liang  1 , Xiangyu Zhang  1
Affiliations

Role of Programmed Cell Death 4 (PDCD4)-Mediated Akt Signaling Pathway in Vascular Endothelial Cell Injury Caused by Lower-Extremity Ischemia-Reperfusion in Rats

Huanhuan Chen et al. Med Sci Monit. .

Abstract

BACKGROUND We aimed to investigate the role of PDCD4-mediated Akt signaling pathway in vascular endothelial cell injury caused by ischemia-reperfusion in the lower extremities. MATERIAL AND METHODS Ten rats were used as control, while 50 rats were used for creating disease models and were assigned to 5 groups: model group (no injection), NC group (injected with vectors containing PDCD negative control sequence), sh-PDCD4 group (injected with vectors containing sh-PDCD4 sequence), IGF-1 group (injected with IGF-1), and sh-PDCD4+IGF-1 group (injected with IGF-1 and vectors containing sh-PDCD4 sequence). RESULTS Compared with the control group, the expression levels of PDCD4 mRNA and protein, as well as levels of circulating endothelial cells, von Willebrand factor, thrombomodulin, and malondialdehyde, increased in the other 5 groups, while the mRNA and protein expression levels of Akt and eNOS, the protein expression levels of p-Akt and p-eNOS, and superoxide dismutase content decreased in these groups (all P<0.05). Compared with the model group, the sh-PDCD4 and sh-PDCD4+1GF-1 groups had lower mRNA and protein expressions of PDCD4 (all P<0.05), whereas the IGF-1 group had similar levels (all P>0.05). These 3 groups had lower levels of circulating endothelial cells, von Willebrand factor, thrombomodulin, and malondialdehyde, and higher mRNA and protein expressions of Akt and eNOS, protein expressions of p-Akt and p-eNOS, and superoxide dismutase content (all P<0.05). The NC group did not differ from the model group (all P>0.05). CONCLUSIONS PDCD4 gene silencing can activate the Akt signaling pathway and attenuate vascular endothelial cell injury caused by ischemia-reperfusion in the lower extremities in rats.

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Conflict of interest statement

Conflicts of interest

None.

Figures

Figure 1
Figure 1
Flow diagram of the study. PDCD4 – programmed cell death 4; IGF-1 – insulin-like growth factor 1; CEC – circulating endothelial cell; vWF – von Willebrand factor; SOD – superoxide dismutase; MDA – malondialdehyde.
Figure 2
Figure 2
Comparison of CEC count among each group. * P<0.05 vs. the control group, # P<0.05 vs. the model group, & P<0.05 vs. the sh-PDCD4 group. CEC – circulating endothelial cell; PDCD4 – programmed cell death 4; IGF-1 – insulin-like growth factor 1.
Figure 3
Figure 3
Comparison of TM and vWF levels among groups. (A) TM level in each group. (B) vWF level in each group. * P<0.05 vs. control group, # P<0.05 vs. model group, & P<0.05 vs. sh-PDCD4 group. TM – thrombomodulin; vWF – von Willebrand factor; PDCD4 – programmed cell death 4; IGF-1 – insulin-like growth factor 1.
Figure 4
Figure 4
Comparison of SOD level among groups. * P<0.05 vs. control group, # P<0.05 vs. model group, & P<0.05 vs. sh-PDCD4 group. SOD – superoxide dismutase; PDCD4 – programmed cell death 4; IGF-1 – insulin-like growth factor 1.
Figure 5
Figure 5
Comparison of MDA level among each group. * P<0.05 vs. the control group, # P<0.05 vs. the model group, & P<0.05 vs. the sh-PDCD4 group. PDCD4 – programmed cell death 4; IGF-1 – insulin-like growth factor 1; MDA – malondialde NC.
Figure 6
Figure 6
Comparison of mRNA expressions among groups after transfection. * P<0.05 vs. the control group, # P<0.05 vs. the model group, & P<0.05 vs. the sh-PDCD4 group. PDCD4 – programmed cell death 4; eNOS – endothelial NOS; IGF-1 – insulin-like growth factor 1.
Figure 7
Figure 7
Comparison of protein expression in each group after transfection. (A) Western blot result. (B) protein expression level in each group. * P<0.05 vs. control group, # P<0.05 vs. model group, & P<0.05 vs. sh-PDCD4 group. PDCD4 – programmed cell death 4; eNOS – endothelial NOS; IGF-1 – insulin-like growth factor 1.
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