Osteopontin and fibronectin in lung tissue, serum, and bronchoalveolar lavage fluid of dogs with idiopathic pulmonary fibrosis and control dogs

特发性肺纤维化犬和对照犬的肺组织、血清和支气管肺泡灌洗液中的骨桥蛋白和纤连蛋白

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作者:Aline Fastrès, Elodie Roels, Alexandru C Tutunaru, Géraldine Bolen, Anne-Christine Merveille, Michael J Day, Mutien-Marie Garigliany, Nadine Antoine, Cécile Clercx

Background

Idiopathic pulmonary fibrosis (IPF) affects West Highland white terriers (WHWTs). Osteopontin (SPP1) and fibronectin (FN1) are associated with human IPF and are overexpressed by bronchoalveolar lavage fluid (BALF) macrophages in dogs with IPF.

Conclusions

Results suggest that SPP1 is involved in pathogenesis of IPF and could predispose that breed to the disease. Osteopontin serum concentration could serve as a diagnostic biomarker of IPF.

Methods

Cross-sectional observational study. Immunohistochemistry was used to localize SPP1 and FN1 in lung tissue. Serum and BALF SPP1 and FN1 concentrations were measured using canine ELISA kits and compared between groups.

Objective

To investigate the value of these proteins as biomarkers of IPF. Animals: West Highland white terriers (WHWTs) with IPF, control WHWTs, and terriers.

Results

Osteopontin stained ciliated epithelial cells, smooth muscular cells, and macrophages of all included dogs, and type-II pneumocytes and extracellular matrix of all 12 diseased WHWTs, 4/6 control WHWTs, and none of the 3 terriers. Osteopontin serum concentration was higher in diseased WHWTs (n = 22; 2.15 ng/mL [0.74-5.30]) compared with control WHWTs (n = 13; 0.63 ng/mL [0.41-1.63]; P = .005) and terriers (n = 15; 0.31 ng/mL [0.19-0.51]; P < .0001), and in control WHWTs compared with terriers (P = .005). Osteopontin BALF concentrations were higher in diseased (0.27 ng/mL [0.14-0.43]) and control WHWTs (0.25 ng/mL [0.14-0.40]), compared with terriers (0.02 ng/mL [0.01-0.08]; P < .0001 and P = .003, respectively). Fibronectin (FN1) serum concentrations were lower in diseased dogs (1.03 ng/mL [0.35-1.48]) and control WHWTs (0.61 ng/mL [0.24-0.65]) compared with terriers (2.72 ng/mL [0.15-5.21]; P < .0001 and P = .0001, respectively). There was no difference in FN1 immunostaining and FN1 BALF concentrations between groups. Conclusions: Results suggest that SPP1 is involved in pathogenesis of IPF and could predispose that breed to the disease. Osteopontin serum concentration could serve as a diagnostic biomarker of IPF.

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