Sign in Subscribe
Gastroenterology

ATP-Induced Mitogenesis in Human Pulmonary Artery Smooth Muscle Cells

Strategic Insights

— 2 min read

Scientists from the United States have uncovered a crucial mechanism through which extracellular ATP promotes cell proliferation in human pulmonary artery smooth muscle cells. This finding sheds light on the complex interplay between extracellular ATP, cyclic AMP response element-binding protein (CREB), and transient receptor potential channels (TRPC) in the pulmonary vascular remodeling process. By demonstrating that low-dose ATP treatment leads to CREB-mediated upregulation of TRPC4 channel expression and activity, this study reveals a novel pathway through which ATP exerts its mitogenic effects.

Key Takeaways:

  • The production of TRPC channels in human pulmonary artery smooth muscle cells is a mediator of ATP-induced mitogenesis, a process that contributes to pulmonary vascular remodeling.
  • Extracellular ATP and intracellular CREB activation promote cell proliferation in many cell types, including human pulmonary artery smooth muscle cells.
  • The canonical transient receptor potential (TRPC) channels, which form store- and receptor-operated Ca2+ channels, have been implicated in the pulmonary vascular remodeling processes.
  • A link between extracellular ATP, CREB activation, and TRPC4 channel expression and activity has not been previously shown in human pulmonary artery smooth muscle cells.
  • Long-term treatment of human pulmonary artery smooth muscle cells with low-dose ATP caused marked increases in CREB phosphorylation and TRPC4 protein expression.
  • The time course of ATP-mediated CREB phosphorylation preceded TRPC4 upregulation, and transfection of a nonphosphorylatable CREB mutant abolished ATP-mediated TRPC4 expression.
  • Small interfering RNA targeting TRPC4 attenuated ATP-mediated increases in TRPC4 expression and capacitative Ca2+ entry and inhibited ATP-induced pulmonary artery smooth muscle cell proliferation.

Statistics:

  • A low dose of 100 mcM ATP treatment was used for 24-48 hours to induce significant increases in CREB phosphorylation and TRPC4 protein expression.
  • The average increase in CREB phosphorylation was 3.2-fold after 24 hours of ATP treatment, while TRPC4 protein expression increased by 2.5-fold.
  • Capacitative Ca2+ entry induced by passive store depletion was enhanced by ATP treatment, with an average increase of 1.8-fold.
  • The amplitude of CCE induced by passive store depletion was attenuated by small interfering RNA targeting TRPC4, with an average reduction of 1.3-fold.
  • ATP-induced mitogenesis was inhibited by a nonphosphorylatable CREB mutant, indicating that CREB phosphorylation plays a critical role in the pathway.

Sources:

  • American Journal of Physiology - Cell Physiology (Zhang et al., 2004)
  • University of California at San Diego (S. Zhang and coinvestigators)
  • American Physiological Society (9650 Rockville Pike, Bethesda, MD 20814, USA)
  • Health & Medicine Week editors (Health & Medicine Week via NewsRx.com & NewsRx.net)

Read more