Transforming growth factor β-related genes in human retinal pigment epithelial cells after tacrolimus treatment

Pharmacol Rep. 2016 Oct;68(5):969-74. doi: 10.1016/j.pharep.2016.04.020. Epub 2016 May 11.

Abstract

Background: The transforming growth factor β (TGFβ) family plays an important role in the pathogenesis of many diseases, including fibrotic pathologies of the eyes. The difficulties of surgical procedures contribute to the search for new treatment strategies for proliferative vitreoretinopathy. Therefore, the aim of this study was to investigate the expression profile of TGFβ isoforms, their receptors, and TGFβ-related genes in human retinal pigment epithelial cells (RPE) after tacrolimus (FK-506) treatment in the presence or absence of lipopolysaccharide (LPS)-induced inflammation.

Methods: The expression profile was analyzed using oligonucleotide microarrays and quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) techniques.

Results: Analysis using oligonucleotide microarrays revealed 20 statistically significant differentially expressed TGFβ-related genes after LPS treatment in relation to control cells, and after tacrolimus and LPS treatment in relation to LPS-treated cells. Moreover, our results showed that mRNA levels for TGFβ2 and TGFβR3 after tacrolimus treatment, and for TGFβR3 after tacrolimus and LPS treatment in RPE cells were decreased. In turn, in the presence of LPS-induced inflammation, TGFβ2 mRNA level was increased.

Conclusions: These results can be important in regard to the treatment of proliferative vitreoretinopathy, pathogenesis of which is associated with processes regulated by TGFβ, such as inflammation, proliferation, epithelial-mesenchymal transition (EMT), and fibrosis.

Keywords: Oligonucleotide microarray; Proliferative vitreoretinopathy; Retinal pigment epithelial cells; Tacrolimus; Transforming growth factor β.

MeSH terms

  • Cells, Cultured
  • Epithelial Cells / drug effects*
  • Epithelial-Mesenchymal Transition / drug effects
  • Epithelial-Mesenchymal Transition / genetics
  • Humans
  • Inflammation / drug therapy
  • Inflammation / genetics
  • RNA, Messenger / genetics
  • Retinal Pigment Epithelium / drug effects*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Tacrolimus / pharmacology*
  • Transforming Growth Factor beta / genetics*
  • Vitreoretinopathy, Proliferative / drug therapy
  • Vitreoretinopathy, Proliferative / genetics

Substances

  • RNA, Messenger
  • Transforming Growth Factor beta
  • Tacrolimus