scholarly journals P2‐8: Exosomal micro RNA‐146a derived from human lung fibroblasts could modulate cyclooxygenase 2 gene expression

Respirology ◽  
2021 ◽  
Vol 26 (S3) ◽  
pp. 115-116
Keyword(s):  
Gene Expression ◽  
Human Lung ◽  
Cyclooxygenase 2 ◽  
Micro Rna ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts

Cigarette smoke induces cyclooxygenase-2 and microsomal prostaglandin E2 synthase in human lung fibroblasts: implications for lung inflammation and cancer

2004 ◽  
Vol 287 (5) ◽  
pp. L981-L991 ◽  
Author(s):  
Christine A. Martey ◽  
Stephen J. Pollock ◽  
Chantal K. Turner ◽  
Katherine M. A. O'Reilly ◽  
Carolyn J. Baglole ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Human Lung ◽  
Cyclooxygenase 2 ◽  
Lung Fibroblasts ◽  
Normal Lung ◽  
Prostaglandin E ◽  
Human Lung Fibroblasts ◽  
Eicosanoid Production ◽  
Normal Human ◽  
Cox 2

Cigarette smoking can lead to many human pathologies including cardiovascular and respiratory disease. Recent studies have defined a role for fibroblasts in the development of colon cancer. Moreover, fibroblasts are now thought of as key “sentinel” cells that initiate inflammation by releasing proinflammatory mediators including prostaglandins (PGs). Pathological overexpression of cyclooxygenase-2 (COX-2) and excess eicosanoid production are found in the early stages of carcinogenesis. By promoting chronic inflammation, COX-2 and eicosanoid production may actually cause a predisposition to malignancy. Furthermore, the associated inflammation induced by production of these mediators is central to the pathogenesis of chronic obstructive pulmonary disease. Little is known of the responses of normal lung fibroblasts to cigarette smoke, despite their abundance. We report herein that normal human lung fibroblasts, when exposed to cigarette smoke extract, induce COX-2 with concurrent synthesis of prostaglandin E2 (PGE2). The mechanisms by which cigarette-derived toxicants lead to increased COX-2 levels and PGE2 synthesis include increases in steady-state COX-2 mRNA levels (approximately four- to fivefold), phosphorylation of ERK1/2, and nuclear translocation of the p50 and p65 subunits of the transcription factor NF-κB, which are important elements in COX-2 expression. Furthermore, there was a dramatic 25-fold increase in microsomal prostaglandin E synthase, the key enzyme involved in the production of PGE2. We propose that normal human lung fibroblasts, when exposed to cigarette smoke constituents, elicit COX-2 expression with consequent prostaglandin synthesis, thus creating a proinflammatory environment. This chronic inflammatory state may act as one of the first steps towards epithelial transformation.

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 ◽  
...  
Keyword(s):  
Gene Expression ◽  
Human Lung ◽  
Receptor Gene ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts ◽  
Bradykinin Receptor ◽  
Receptor Gene Expression

scholarly journals Hypoxia-induced preadipocyte factor 1 expression in human lung fibroblasts through ERK/PEA3/c-Jun pathway

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Wun-Hao Cheng ◽  
Chia-Ling Chen ◽  
Jing-Yun Chen ◽  
Chien-Huang Lin ◽  
Bing-Chang Chen
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Promoter Region ◽  
Human Lung ◽  
Mrna Level ◽  
Hypoxia Inducible Factor ◽  
Lung Fibroblasts ◽  
Tissue Fibrosis ◽  
Human Lung Fibroblasts ◽  
Si Rna

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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