ovalbumin and Asthma-Chronic-Obstructive-Pulmonary-Disease-Overlap-Syndrome

Chronic obstructive asthma is characterized by airway fibrosis. Hypoxia and connective tissue growth factor (CTGF) play important roles in airway fibrosis. Preadipocyte factor-1 (Pref-1) participates in adipocyte differentiation and liver fibrosis. Herein, we investigated the role of Pref-1 in airway fibrosis in chronic obstructive asthma. We found that Pref-1 was overexpressed in lung tissues from chronic obstructive asthma patients compared to normal subjects. Extracellular matrix proteins were inhibited by Pref-1 small interfering (si)RNA in airway fibroblasts from chronic obstructive asthma patients. Furthermore, ovalbumin induced prominent Pref-1 expression and fibronectin coexpression. Hypoxia induced Pref-1 upregulation and its release into medium of WI-38 cells. Hypoxia-induced CTGF expression was inhibited by Pref-1 siRNA. We also found that Pref-1-stimulated fibrotic protein expressions were reduced by ATN-161, curcumin, U0126, and c-Jun siRNA in WI-38. Furthermore, ATN161 inhibited Pref-1-induced ERK phosphorylation, and ITGA5 siRNA inhibited c-Jun phosphorylation. Moreover, expression of CTGF, Fibronectin, α-SMA, and ERK and c-Jun phosphorylation were all increased in fibroblasts from patients with chronic obstructive asthma. Taken together, these results suggest that Pref-1 participates in airway fibrosis and hypoxia-induced CTGF expression via the integrin receptor α5β1/ERK/AP-1 pathway.

Topics: Animals; Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome; Biopsy; Calcium-Binding Proteins; Case-Control Studies; Cell Differentiation; Cell Hypoxia; Cell Line; Connective Tissue Growth Factor; Disease Models, Animal; Female; Fibroblasts; Fibrosis; Healthy Volunteers; Humans; Integrin alpha5beta1; Lung; MAP Kinase Signaling System; Membrane Proteins; Mice; Mitogen-Activated Protein Kinase 3; Ovalbumin; Transcription Factor AP-1; Up-Regulation