Cigarette smoke extract induced rat pulmonary artery smooth muscle cells proliferation via PKCα-mediated cyclin D1 expression

J Cell Biochem. 2011 Aug;112(8):2082-8. doi: 10.1002/jcb.23131.

Abstract

Cigarette smoke could induce pulmonary smooth muscle cells (PASMCs) proliferation. Although our previous study had implied the involvement of protein kinase Cα (PKCα), the molecular mechanism underlying PKCα pathway in this process is still unknown. In this study, rat PASMCs were stimulated by cigarette smoke extract (CSE) or PMA (a special activator to PKCα). Two percent CSE and PMA significantly enhanced cyclin D1 expression and cells proliferation. But cyclin D1-specific siRNA successfully inhibited DNA synthesis in CSE-treated or PMA-treated cells. On the other hand, PKCα-specific siRNA significantly suppressed cyclin D1 expression in CSE-treated cells. Moreover, PKCα-specific siRNA resulted in a cell-cycle arrest in G0/G1 and decreased cells number significantly. We conclude that CSE induced rat PASMCs proliferation at least partly via PKCα-mediated cyclin D1 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogens / pharmacology
  • Cells, Cultured
  • Complex Mixtures / adverse effects
  • Complex Mixtures / pharmacology*
  • Cyclin D1 / biosynthesis*
  • Enzyme Activators / pharmacology
  • G1 Phase / drug effects*
  • Gene Expression Regulation / drug effects*
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / pathology
  • Myocytes, Smooth Muscle / metabolism*
  • Myocytes, Smooth Muscle / pathology
  • Protein Kinase C-alpha / metabolism*
  • Pulmonary Artery / metabolism*
  • Pulmonary Artery / pathology
  • Rats
  • Rats, Wistar
  • Resting Phase, Cell Cycle / drug effects*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tobacco Smoke Pollution*

Substances

  • Carcinogens
  • Ccnd1 protein, rat
  • Complex Mixtures
  • Enzyme Activators
  • Tobacco Smoke Pollution
  • Cyclin D1
  • Protein Kinase C-alpha
  • Tetradecanoylphorbol Acetate