TY - JOUR
T1 - Pref-1 induced lung fibroblast differentiation by hypoxia through integrin α5β1/ERK/AP-1 cascade
AU - Cheng, Wun Hao
AU - Lee, Kang Yun
AU - Yu, Ming Chih
AU - Chen, Jing Yun
AU - Lin, Chien Huang
AU - Chen, Bing Chang
N1 - Funding Information:
This study was supported by grants ( MOST108-2320-B-038-0068 ) from the Ministry of Science and Technology of Taiwan , R.O.C.
Publisher Copyright:
© 2021
PY - 2021/10/15
Y1 - 2021/10/15
N2 - 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.
AB - 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.
KW - Airway fibrosis
KW - Chronic obstructive asthma
KW - Hypoxia
KW - Integrin receptor α5β1
KW - Pref-1
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U2 - 10.1016/j.ejphar.2021.174385
DO - 10.1016/j.ejphar.2021.174385
M3 - Article
C2 - 34331953
AN - SCOPUS:85111499333
SN - 0014-2999
VL - 909
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
M1 - 174385
ER -