Role of PTEN in Regulating Autophagy via the Nrf2/HO-1 Pathway in Aortic Medial Degeneration
Objective To investigate the mechanisms of phosphatase and tension homolog(PTEN)in aortic medial degeneration(AMD).Methods Three weeks C57BL/6J mice were randomly divided into control group,AMD group,smPTEN+AMD group,smPTEN+AMD+3-Methyladenin(3-MA)(smPTEN+AMD+3-MA group),PTEN+AMD+Nrf2silencing group(smPTEN+AMD+shNrf2group).The vascular structure and disruption of elastic fiber were observed through hematoxylin-eosin and EVG staining,reactive oxygen species(ROS)was measured by immunofluorescence,inflammatory factors were detected by enzyme-linked immunosor-bent assay(ELISA),autophagy-related proteins and Nrf2/HO-1 pathway proteins was examined by western blot,autophagosome was observed by electron microscopy.Results Compared with control group,AMD group exhibited an increased thickness of vascular wall accompanied by tumor-like expansion,an increase in ROS,IL-6,IL-1 β,TNF-α,LC3 Ⅱ/I,Beclin-1,autophagosomes,PTEN,while p62(SQSTM1),Nrf2(nuclear factor erythroid 2-related factor 2),HO-1(heme oxygenase 1)were decreased(P＜0.05).Compared with AMD group,smPTEN+AMD group showed that the vascular wall thickened,a decrease in ROS,IL-6,IL-1 β,TNF-α,LC3 Ⅱ/Ⅰ,Beclin-1,autophagosomes,PTEN,an increase in p62,Nrf2,HO-1(P＜0.05).Compared with smPTEN+AMD group,smPTEN+AMD+3-MA group displayed a relatively intact vascular structure,a decrease in ROS,IL-6,IL-1 β,TNF-α,LC3 Ⅱ/Ⅰ,Beclin-1,and autophagosomes,while p62,Nrf2,and HO-1 were increased(P＜0.05),and PTEN showed no significant change(P＞0.05);While smPTEN+AMD+shNrf2group exhibited a significant increase in vascular wall thickness with the formation of false lumens,an increase in ROS,IL-6,IL-1 β,TNF-α,LC3 Ⅱ/Ⅰ,Beclin-1,autophagosomes,with a decrease in p62,Nrf2 and HO-1(P＜0.05),and PTEN showed no significant change(P＞0.05).Conclusion PTEN can promote the development of AMD by activating autophagy,exacerbating oxidative stress and inflammatory responses though inhibiting Nrf2/HO-1 pathway.
万方数据
维普
