Downregulation of Talin-1 expression associates with increased proliferation and migration of vascular smooth muscle cells in aortic dissection

BMC Cardiovasc Disord. 2017 Jun 20;17(1):162. doi: 10.1186/s12872-017-0588-0.

Abstract

Background: This study aimed to assessed whether Talin-1 is involved in the pathogenesis of aortic dissection via regulating vascular smooth muscle cell (VSMC) biological function.

Methods: Human aortic samples were obtained from organ donors who died from nonvascular diseases as normal controls and from patients undergoing surgical repair of thoracic aortic dissection. The expression level and distribution of Talin-1 were detected using westernblot analysis and immunohistochemistry in each sample. We inhibited the expression of Talin-1 via RNA interference in VSMCs. VSMC proliferation was detected by Cell-counting Kit-8 analyses. Scratch test and flow cytometry were used to identify the migration and apoptosis ability. Antibody microarray analysis and qRT-PCR were used to detect some protein and mRNA changes which were induced by Talin-1 downregulation.

Results: Talin-1 was significantly downregulated in the media of aortic dissection samples compared with controls (P < 0.05). Talin-1 knockdown significantly induced VSMC proliferation and migration in vitro. Proteins which involved in cell cycle can be regulated by downregulating Talin-1. Down regulation of Talin-1 can significanly increased the expression of anaphase-promoting complex subunit 2 (APC2) and decreased p19 alternative reading frame (p19ARF), Cullin-3, and beta actin's expression.

Conclusions: Talin-1 induces VSMCs proliferation and migration. It downregulated in aortic dissection, which might play a potential role in the development of aortic dissection.

Keywords: Aortic dissection; Migration; Proliferation; Talin-1; Vascular smooth muscle cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aorta, Thoracic / metabolism
  • Aorta, Thoracic / pathology
  • Aortic Aneurysm, Thoracic / genetics
  • Aortic Aneurysm, Thoracic / metabolism*
  • Aortic Aneurysm, Thoracic / pathology
  • Aortic Dissection / genetics
  • Aortic Dissection / metabolism*
  • Aortic Dissection / pathology
  • Apoptosis
  • Case-Control Studies
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Movement*
  • Cell Proliferation*
  • Cells, Cultured
  • Down-Regulation
  • Female
  • Humans
  • Male
  • Middle Aged
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / pathology
  • Myocytes, Smooth Muscle / metabolism*
  • Myocytes, Smooth Muscle / pathology
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Talin / genetics
  • Talin / metabolism*
  • Time Factors
  • Transfection

Substances

  • Cell Cycle Proteins
  • RNA, Messenger
  • TLN1 protein, human
  • Talin