Lin28a up-regulation is associated with the formation of restenosis via promoting proliferation and migration of vascular smooth muscle cells

J Cell Mol Med. 2020 Sep;24(17):9682-9691. doi: 10.1111/jcmm.15506. Epub 2020 Jul 25.

Abstract

To explore the potential role of Lin28a in the development of restenosis after percutaneous transluminal angioplasty, double-balloon injury surgery and mono-balloon injury surgery were used to establish restenosis and atherosclerosis models, respectively, so as to better distinguish restenosis from atherosclerotic lesions. Immunohistochemical analysis revealed that significantly higher expression of Lin28a was observed in the iliac arteries of restenosis plaques than that of atherosclerosis plaques. Immunofluorescence studies showed the colocalization of Lin28a with α-smooth muscle actin in restenosis plaques, rather than in atherosclerosis plaques, which suggested that Lin28a might be related to the unique behaviour of vascular smooth muscle cells (VSMCs) in restenosis. To further confirm above hypothesis, Lin28a expression was up-regulated by transfection of Lenti-Lin28a and inhibited by Lenti-Lin28a-shRNA transfection in cultured VSMCs, and then the proliferation and migration capability of VSMCs were detected by EdU and Transwell assays, respectively. Results showed that the proliferation and migration of VSMCs were significantly increased in accordance with the up-regulation of Lin28a expression, while above behaviours of VSMCs were significantly suppressed after inhibiting the expression of Lin28a. In conclusion, the up-regulation of Lin28a exerts its modulatory effect on VSMCs' proliferation and migration, which may play a critical role in contributing to pathological formation of restenosis.

Keywords: Lin28a; migration; percutaneous transluminal angioplasty; proliferation; restenosis; vascular smooth muscle cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angioplasty / methods
  • Animals
  • Atherosclerosis / genetics
  • Cell Movement / genetics*
  • Cell Proliferation / genetics*
  • Cells, Cultured
  • Male
  • Muscle, Smooth, Vascular / physiology*
  • Myocytes, Smooth Muscle / physiology*
  • Plaque, Atherosclerotic / genetics
  • RNA-Binding Proteins / genetics*
  • Rats
  • Rats, Sprague-Dawley
  • Transfection / methods
  • Up-Regulation / genetics*

Substances

  • Lin28A protein, rat
  • RNA-Binding Proteins