Decreased airway expression of vascular endothelial growth factor in cigarette smoke-induced emphysema in mice and COPD patients

Masaru Suzuki, Tomoko Betsuyaku, Katsura Nagai, Satoshi Fuke, Yasuyuki Nasuhara, Kichizo Kaga, Satoshi Kondo, Ichiro Hamamura, Junko Hata, Hiroshi Takahashi, Masaharu Nishimura

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF) signaling is crucial for lung structure maintenance. Although VEGF deficiency plays a role in the pathogenesis of emphysema in animals, little is known about VEGF expression levels and functions, as well as VEGF receptors, in airway epithelial cells, which are in direct contact with the environment. In this study, C57BL/6J mice were exposed to cigarette smoke (CS) for short (∼ 10 days) and long (4-24 wk) time periods, and bronchiolar expressions of VEGF and its receptors VEGFR-1 and VEGFR-2 were examined. The relationships between the expressions of VEGF, VEGFR-1, and VEGFR-2 and smoking histories and/or chronic obstructive pulmonary disease (COPD) were examined in humans. The mRNA levels were quantified in bronchiolar epithelium harvested by laser capture microdissection in both mouse and human lung tissues or in human bronchial epithelium harvested by bronchoscopic brushing. The VEGF protein level was assessed by immunohistochemistry or enzyme-linked immunosorbent assay. Repeated CS exposure downregulated bronchiolar expressions of VEGF and both VEGF receptors at various time points prior to the development of emphysema. In humans, bronchiolar VEGF was significantly decreased in smokers with COPD compared to lifelong nonsmokers, as well as to smokers without COPD; however, there was no difference in bronchiolar VEGF levels between lifelong nonsmokers and smokers without COPD. On the other hand, bronchiolar VEGFR-2 was downregulated in smokers with and without COPD compared to lifelong nonsmokers. These findings suggest the association of downregulation of bronchiolar VEGF and its receptors with cigarette smoking and COPD.

Original languageEnglish
Pages (from-to)349-359
Number of pages11
JournalInhalation Toxicology
Volume20
Issue number3
DOIs
Publication statusPublished - 2008 Feb
Externally publishedYes

Fingerprint

Pulmonary diseases
Emphysema
Smoke
Tobacco Products
Chronic Obstructive Pulmonary Disease
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor
Vascular Endothelial Growth Factor Receptor-2
Vascular Endothelial Growth Factor Receptor-1
Down-Regulation
Microdissection
Epithelium
Smoking
Laser Capture Microdissection
Lung
Immunosorbents
Inbred C57BL Mouse
Assays
Animals
Epithelial Cells

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Decreased airway expression of vascular endothelial growth factor in cigarette smoke-induced emphysema in mice and COPD patients. / Suzuki, Masaru; Betsuyaku, Tomoko; Nagai, Katsura; Fuke, Satoshi; Nasuhara, Yasuyuki; Kaga, Kichizo; Kondo, Satoshi; Hamamura, Ichiro; Hata, Junko; Takahashi, Hiroshi; Nishimura, Masaharu.

In: Inhalation Toxicology, Vol. 20, No. 3, 02.2008, p. 349-359.

Research output: Contribution to journalArticle

Suzuki, M, Betsuyaku, T, Nagai, K, Fuke, S, Nasuhara, Y, Kaga, K, Kondo, S, Hamamura, I, Hata, J, Takahashi, H & Nishimura, M 2008, 'Decreased airway expression of vascular endothelial growth factor in cigarette smoke-induced emphysema in mice and COPD patients', Inhalation Toxicology, vol. 20, no. 3, pp. 349-359. https://doi.org/10.1080/08958370701866412
Suzuki, Masaru ; Betsuyaku, Tomoko ; Nagai, Katsura ; Fuke, Satoshi ; Nasuhara, Yasuyuki ; Kaga, Kichizo ; Kondo, Satoshi ; Hamamura, Ichiro ; Hata, Junko ; Takahashi, Hiroshi ; Nishimura, Masaharu. / Decreased airway expression of vascular endothelial growth factor in cigarette smoke-induced emphysema in mice and COPD patients. In: Inhalation Toxicology. 2008 ; Vol. 20, No. 3. pp. 349-359.
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