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Author Notes:

Address correspondence to:Kathy K. Griendling, Emory University, Division of Cardiology, 101 Woodruff Circle, 308 WMB, Atlanta, GA 30322, Telephone: 404-727-3364, Fax: 404-727-3585, kgriend@emory.edu

The authors have no conflicts of interest to report.

Subjects:

Research Funding:

This work was supported by NIH grants HL38206 and HL095070.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Medicine, Research & Experimental
  • Pathology
  • Research & Experimental Medicine
  • DELTA-INTERACTING PROTEIN-2
  • DNA-POLYMERASE-DELTA
  • CYCLIN-DEPENDENT KINASES
  • CELL NUCLEAR ANTIGEN
  • REACTIVE OXYGEN
  • NADPH OXIDASE
  • NOX4
  • BINDING
  • ARREST
  • DEGRADATION

Poldip2 knockdown inhibits vascular smooth muscle proliferation and neointima formation by regulating the expression of PCNA and p21

Tools:

Journal Title:

Laboratory Investigation

Volume:

Volume 99, Number 3

Publisher:

, Pages 387-398

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Polymerase delta-interacting protein 2 (Poldip2) is a multi-functional protein with numerous roles in the vasculature, including the regulation of cell apoptosis and migration, as well as extracellular matrix deposition; however, its role in VSMC proliferation and neointimal formation is unknown. In this study, we investigated the role of Poldip2 in intraluminal wire-injury induced neointima formation and proliferation of vascular smooth muscle cells in vitro and in vivo. Poldip2 expression was observed in the intima and media of human atherosclerotic arteries, where it colocalized with proliferating cell nuclear antigen (PCNA). Wire injury of femoral arteries of Poldip2 +/+ mice induced robust neointimal formation after 2 weeks, which was impaired in Poldip2 +/‒ mice. PCNA expression was significantly reduced and expression of the cell cycle inhibitor p21 was significantly increased in wire-injured arteries of Poldip2 +/‒ animals compared to wild-type controls. No difference was observed in apoptosis. Downregulation of Poldip2 in rat aortic smooth muscle cells significantly reduced serum-induced proliferation and PCNA expression, but upregulated p21 expression. Downregulation of p21 using siRNA reversed the inhibition of proliferation induced by knockdown of Poldip2. These results indicate that Poldip2 plays a critical role in the proliferation of VSMCs.

Copyright information:

© 2018, United States & Canadian Academy of Pathology.

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