Regulation of bradykinin receptor gene expression in human lung fibroblasts

2000 ◽  
Vol 397 (2-3) ◽  
pp. 237-246 ◽  
Author(s):  
Stephen B. Phagoo ◽  
Mohammed Yaqoob ◽  
Esteban Herrera-Martinez ◽  
Peter McIntyre ◽  
Caroline Jones ◽  
...  
1996 ◽  
Vol 33 (1-3) ◽  
pp. 9-15 ◽  
Author(s):  
Yuh-Jiin Ivy Jong ◽  
Linda R. Dalemar ◽  
Beverly Wilhelm ◽  
Nancy Lewis Baenziger

1997 ◽  
Vol 25 (1) ◽  
pp. 43S-43S ◽  
Author(s):  
STEPHEN B. PHAGOO ◽  
MOHAMMED YAQOOB ◽  
PETER McINTYRE ◽  
CAROLINE JONES ◽  
GILLIAN M. BURGESS

1992 ◽  
Vol 152 (3) ◽  
pp. 478-485 ◽  
Author(s):  
Tibor Szentendrei ◽  
Eliane Lazar-Wesley ◽  
Tokio Nakane ◽  
Mridulika Virmani ◽  
George Kunos

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Wun-Hao Cheng ◽  
Chia-Ling Chen ◽  
Jing-Yun Chen ◽  
Chien-Huang Lin ◽  
Bing-Chang Chen

Abstract Background Several studies have reported that hypoxia plays a pathological role in severe asthma and tissue fibrosis. Our previous study showed that hypoxia induces A disintegrin and metalloproteinase 17 (ADAM17) expression in human lung fibroblasts. Moreover, preadipocyte factor 1 (Pref-1) is cleaved by ADAM17, which participates in adipocyte differentiation. Furthermore, Pref­1 overexpression is involved in tissue fibrosis including liver and heart. Extracellular signal-regulated kinase (ERK) could active downstram gene expression through polyoma enhancer activator 3 (PEA3) phosphorylation. Studies have demonstrated that PEA3 and activator protein 1 (AP-1) play crucial roles in lung fibrosis, and the Pref-1 promoter region contains PEA3 and AP-1 binding sites as predicted. However, the roles of ERK, PEA3, and AP-1 in hypoxia-stimulated Pref-1 expression in human lung fibroblasts remain unknown. Methods The protein expression in ovalbumin (OVA)-induced asthmatic mice was performed by immunohistochemistry and immunofluorescence. The protein expression or the mRNA level in human lung fibroblasts (WI-38) was detected by western blot or quantitative PCR. Small interfering (si) RNA was used to knockdown gene expression. The collaboration with PEA3 and c-Jun were determined by coimmunoprecipitation. Translocation of PEA3 from the cytosol to the nucleus was observed by immunocytochemistry. The binding ability of PEA3 and AP-1 to Pref-1 promoter was assessed by chromatin immunoprecipitation. Results Pref-1 and hypoxia-inducible factor 1α (HIF-1α) were expressed in the lung sections of OVA-treated mice. Colocalization of PEA3 and Fibronectin was detected in lung sections from OVA-treated mice. Futhermore, Hypoxia induced Pref­1 protein upregulation and mRNA expression in human lung fibroblasts (WI­38 cells). In 60 confluent WI-38 cells, hypoxia up-regulated HIF-1α and Pref-1 protein expression. Moreover, PEA3 small interfering (si) RNA decreased the expression of hypoxia-induced Pref­1 in WI­38 cells. Hypoxia induced PEA3 phosphorylation, translocation of PEA3 from the cytosol to the nucleus, PEA3 recruitment and AP-1 binding to the Pref­1 promoter region, and PEA3-luciferase activity. Additionally, hypoxia induced c-Jun-PEA3 complex formation. U0126 (an ERK inhibitor), curcumin (an AP­1 inhibitor) or c-Jun siRNA downregulated hypoxia-induced Pref-1 expression. Conclusions These results implied that ERK, PEA3, and AP­1 participate in hypoxia­induced Pref­1 expression in human lung fibroblasts.


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