Transforming Growth Factor Beta 1 Activation, Storage, and Signaling Pathways in Idiopathic Pulmonary Fibrosis in Dogs

E. Krafft*, P. Lybaert, E. Roels, H. P. Laurila, M. M. Rajamaki, F. Farnir, M. Myllarniemi, M. J. Day, K. Mc Entee, C. Clercx

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

22 Citations (Scopus)

Abstract

BackgroundThe pathogenesis of idiopathic pulmonary fibrosis (IPF) in dogs is poorly understood. In human, transforming growth factor 1 (TGF-1) is considered central in the pathogenesis.

ObjectivesTo investigate TGF-1 pathway in IPF.

AnimalsLung tissues from 12 affected and 11 control dogs. Serum from 16 affected West Highland white Terriers (WHWTs) and healthy dogs from predisposed (13 WHWTs, 12 Scottish Terriers and 13 Bichons Frise) and nonpredisposed breeds (10 Whippets, 10 Belgian shepherds, 8 Labradors).

MethodsIn this prospective study, immunohistochemistry was used to evaluate expression and localization of TGF-1 protein and proteins involved in TGF-1 signaling (TGF- receptor type I and phospho-Smad2/3). Pulmonary expression of TGF-1 and molecules involved in its storage (latent TGF- binding proteins [LTBP] 1, 2, and 4), activation (6 and 8 integrins, thrombospondin-1) and signal inhibition (Smad 7) was analyzed by quantitative reverse transcriptase PCR. Circulating TGF-1 concentration was measured by ELISA.

ResultsIn IPF, high level of TGF-1 protein was found in areas of fibrosis, epithelial cells had strong expression of TGF- receptor type 1 and phospho-Smad2/3, gene expression was decreased for LTBP 4 (P=.009) and 8 integrin (P

Conclusions and Clinical ImportanceThis study identified an enhanced TGF-1 signaling activity in IPF. TGF-1 storage and activation proteins with altered expression represent potential therapeutic targets. Higher circulating TGF-1 concentration in predisposed breeds might partly explain their susceptibility for IPF.

Original languageEnglish
Pages (from-to)1666-1675
Number of pages10
JournalJournal of Veterinary Internal Medicine
Volume28
Issue number6
DOIs
Publication statusPublished - 2014

Keywords

  • Integrin
  • Latent binding protein
  • Smads
  • Thrombospondin-1
  • HIGHLAND WHITE TERRIERS
  • LATENT TGF-BETA
  • GENE-EXPRESSION
  • INTERSTITIAL PNEUMONIA
  • EPITHELIAL-CELLS
  • DISEASE
  • GROWTH-FACTOR-BETA-1
  • THROMBOSPONDIN-1
  • TGF-BETA-1
  • INFLAMMATION

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