Osthole decreases collagen I/III contents and their ratio in TGF-β1-overexpressed mouse cardiac fibroblasts through regulating the TGF-β/Smad signaling pathway

Chin J Nat Med. 2018 May;16(5):321-329. doi: 10.1016/S1875-5364(18)30063-3.

Abstract

The present study was designed to elucidate whether the mechanism by which osthole decreases collagenI/III contents and their ratio is regulating the TGF-β/Smad signaling pathway in TGF-β1-overexpressed mouse cardiac fibroblasts (CFs). These CFs were cultured and treated with different concentrations of osthole. Our results showed that the TGF-β1 expression in the CFs transfected with that the recombinant expression plasmids pcDNA3.1(+)-TGF-β1 was significantly enhanced. After the CFs were treated with 1.25-5 μg·mL-1 of osthole for 24 h, the mRNA and protein expression levels of collagensIand III were reduced. The collagen I/III ratio was also reduced. The mRNA and protein expression levels of TGF-β1, TβRI, Smad2/3, P-Smad2/3, Smad4, and α-SMA were decreased, whereas the expression level of Smad7 was increased. These effects suggested that osthole could inhibit collagen I and III expression and reduce their ratio via the TGF-β/Smad signaling pathway in TGF-β1 overexpressed CFs. These effects of osthole may play beneficial roles in the prevention and treatment of myocardial fibrosis.

Keywords: Collagen; Mouse cardiac fibroblasts; Osthole; TGF-β1.

MeSH terms

  • Actins / genetics
  • Animals
  • Cells, Cultured
  • Collagen / biosynthesis
  • Collagen / genetics*
  • Coumarins / pharmacology*
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Gene Expression Regulation / drug effects
  • Mice
  • Myocardium / cytology*
  • Protein Serine-Threonine Kinases / genetics
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Transforming Growth Factor beta / genetics
  • Signal Transduction / drug effects*
  • Smad Proteins / genetics*
  • Transforming Growth Factor beta1 / genetics*

Substances

  • Acta2 protein, mouse
  • Actins
  • Coumarins
  • RNA, Messenger
  • Receptors, Transforming Growth Factor beta
  • Smad Proteins
  • Transforming Growth Factor beta1
  • Collagen
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type I