Sonodynamic Therapy Inhibits Fibrogenesis in Rat Cardiac Fibroblasts Induced by TGF-β1

Cell Physiol Biochem. 2016;40(3-4):579-588. doi: 10.1159/000452571. Epub 2016 Nov 25.

Abstract

Background/aims: Sonodynamic therapy (SDT) is a localized ultrasound-activated therapy for atherosclerosis when combined with a sonosensitizer, 5-aminolevulinic acid (ALA), but whether it can prevent cardiac fibrosis has not been studied. In the present study, we evaluated the effects SDT on fibrogenesis in rat cardiac fibroblasts.

Methods: The primary cardiac fibroblasts were isolated from rats, and induced to fibrogenesis with TGF-β1. With this in vitro model, we tested the preventive effects of SDT on fibrogenesis and further the underlying mechanism.

Results: TGF-β1 stimulation up-regulated α-SMA and COLI/III protein levels in cardiac fibroblasts, and enhanced the progression of cells from the G0/G1 phase to the S phase. SDT inhibited the TGF-β1 mediated cell proliferation and decreased the levels of α-SMA and COLI/III by activating AKT/GSK3β pathway and blocking TGF-β1/SMAD3 signaling.

Conclusion: Our studies demonstrate an antifibrotic effect of SDT in rat cardiac fibroblasts, suggesting that SDT may intervene cardiac fibrogenesis by regulating myocardial fibrotic remodeling.

MeSH terms

  • Aminolevulinic Acid / pharmacology
  • Animals
  • Animals, Newborn
  • Cell Cycle / drug effects
  • Cell Death / drug effects
  • Cell Line, Transformed
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Collagen / biosynthesis
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Fibrosis
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Intracellular Space / metabolism
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Protoporphyrins / pharmacology
  • Rats, Sprague-Dawley
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta1 / pharmacology*
  • Ultrasonics*

Substances

  • Protoporphyrins
  • Smad3 Protein
  • Transforming Growth Factor beta1
  • Aminolevulinic Acid
  • Collagen
  • protoporphyrin IX
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt