Reference : Transforming Growth Factor Beta 1 Activation, Storage, and Signaling Pathways in Idio...
Scientific journals : Article
Life sciences : Veterinary medicine & animal health
http://hdl.handle.net/2268/196645
Transforming Growth Factor Beta 1 Activation, Storage, and Signaling Pathways in Idiopathic Pulmonary Fibrosis in Dogs.
English
Krafft, Emilie []
Lybaert, P. []
Roels, Elodie mailto [Université de Liège > Dép. clinique des animaux de compagnie et des équidés (DCA) > Pathologie médicale des petits animaux >]
Laurila, H.P. []
Rajamaki, M.M. []
Farnir, Frédéric [Université de Liège > Département des productions animales (DPA) > Biostatistiques et bioinformatique appliquées aux sc. vétér. >]
Myllarniemi, M. []
Day, M.J. []
Mc Entee, Kathleen [Université de Liège > Dép. clinique des animaux de compagnie et des équidés (DCA) > Pathologie médicale des petits animaux >]
Clercx, Cécile mailto [Université de Liège > Dép. clinique des animaux de compagnie et des équidés (DCA) > Pathologie médicale des petits animaux >]
2014
Journal of Veterinary Internal Medicine
Wiley
28
1666-1675
Yes (verified by ORBi)
International
0891-6640
1939-1676
[en] integrin ; latent binding protein ; smads
[en] BACKGROUND: The pathogenesis of idiopathic pulmonary fibrosis (IPF) in dogs is poorly understood. In human, transforming growth factor beta1 (TGF-beta1) is considered central in the pathogenesis. OBJECTIVES: To investigate TGF-beta1 pathway in IPF. ANIMALS: Lung 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). METHODS: In this prospective study, immunohistochemistry was used to evaluate expression and localization of TGF-beta1 protein and proteins involved in TGF-beta1 signaling (TGF-beta receptor type I and phospho-Smad2/3). Pulmonary expression of TGF-beta1 and molecules involved in its storage (latent TGF-beta binding proteins [LTBP] 1, 2, and 4), activation (alphanubeta6 and alphanubeta8 integrins, thrombospondin-1) and signal inhibition (Smad 7) was analyzed by quantitative reverse transcriptase PCR. Circulating TGF-beta1 concentration was measured by ELISA. RESULTS: In IPF, high level of TGF-beta1 protein was found in areas of fibrosis, epithelial cells had strong expression of TGF-beta receptor type 1 and phospho-Smad2/3, gene expression was decreased for LTBP 4 (P = .009) and beta8 integrin (P < .001) and increased for thrombospondin-1 (P = .016); no difference was seen for Smad7, LTBP1 and 2. Serum TGF-beta1 concentration was higher in predisposed compared with nonpredisposed breeds (P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: This study identified an enhanced TGF-beta1 signaling activity in IPF. TGF-beta1 storage and activation proteins with altered expression represent potential therapeutic targets. Higher circulating TGF-beta1 concentration in predisposed breeds might partly explain their susceptibility for IPF
http://hdl.handle.net/2268/196645
10.1111/jvim.12432

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