Soluble epoxide hydrolase inhibitor 1-trifluoromethoxyphenyl-3- (1-propionylpiperidin-4-yl) urea attenuates bleomycin-induced pulmonary fibrosis in mice

Yong Zhou, Guo Ying Sun, Tian Liu, Jia Xi Duan, Hui Fang Zhou, Kin Sing Lee, Bruce D. Hammock, Xiang Fang, Jian Xin Jiang, Cha Xiang Guan

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Epoxyeicosatrienoic acids (EETs), the metabolites of arachidonic acid derived from the cytochrome P450 (CYP450) epoxygenases, are mainly metabolized by soluble epoxide hydrolase (sEH) to their corresponding diols. EETs but not their diols, have anti-inflammatory properties and inhibition of sEH might provide protective effects against inflammatory fibrosis. We test the effects of a selected sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), on bleomycin-induced pulmonary fibrosis (PF) in mice. A mouse model of PF was established by intratracheal injection of bleomycin and TPPU was administered for 21 days after bleomycin injection. We found TPPU treatment improved the body weight loss and survival rate of bleomycin-stimulated mice. Histological examination showed that TPPU treatment alleviated bleomycin-induced inflammation and maintained the alveolar structure of the pulmonary tissues. TPPU also decreased the bleomycin-induced deposition of collagen and the expression of procollagen I mRNA in lung tissues of mice. TPPU decreased the transforming growth factor-β1 (TGF-β1), interleukin-1β (IL-1β) and IL-6 levels in the serum of bleomycin-stimulated mice. Furthermore, TPPU inhibited the proliferation and collagen synthesis of mouse fibroblasts and partially reversed TGF-β1-induced α-smooth muscle actin expression. Our results indicate that the inhibition of sEH attenuates bleomycin-induced inflammation and collagen deposition and therefore prevents bleomycin-induced PF in a mouse model.

Original languageEnglish (US)
Pages (from-to)399-409
Number of pages11
JournalCell and Tissue Research
Volume363
Issue number2
DOIs
StatePublished - Feb 1 2016

Fingerprint

Epoxide Hydrolases
Pulmonary Fibrosis
Bleomycin
Urea
Collagen
Transforming Growth Factors
Inflammation
Procollagen
Lung
Injections
Interleukin-1
Arachidonic Acid
Cytochrome P-450 Enzyme System
Smooth Muscle
Actins
Weight Loss
Interleukin-6
Fibrosis
Anti-Inflammatory Agents
Fibroblasts

Keywords

  • Epoxyeicosatrienoic acids
  • Mouse
  • Proliferation
  • Pulmonary fibrosis
  • Soluble epoxide hydrolase inhibitor

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cell Biology
  • Histology

Cite this

Soluble epoxide hydrolase inhibitor 1-trifluoromethoxyphenyl-3- (1-propionylpiperidin-4-yl) urea attenuates bleomycin-induced pulmonary fibrosis in mice. / Zhou, Yong; Sun, Guo Ying; Liu, Tian; Duan, Jia Xi; Zhou, Hui Fang; Lee, Kin Sing; Hammock, Bruce D.; Fang, Xiang; Jiang, Jian Xin; Guan, Cha Xiang.

In: Cell and Tissue Research, Vol. 363, No. 2, 01.02.2016, p. 399-409.

Research output: Contribution to journalArticle

Zhou, Yong ; Sun, Guo Ying ; Liu, Tian ; Duan, Jia Xi ; Zhou, Hui Fang ; Lee, Kin Sing ; Hammock, Bruce D. ; Fang, Xiang ; Jiang, Jian Xin ; Guan, Cha Xiang. / Soluble epoxide hydrolase inhibitor 1-trifluoromethoxyphenyl-3- (1-propionylpiperidin-4-yl) urea attenuates bleomycin-induced pulmonary fibrosis in mice. In: Cell and Tissue Research. 2016 ; Vol. 363, No. 2. pp. 399-409.
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AU - Sun, Guo Ying

AU - Liu, Tian

AU - Duan, Jia Xi

AU - Zhou, Hui Fang

AU - Lee, Kin Sing

AU - Hammock, Bruce D.

AU - Fang, Xiang

AU - Jiang, Jian Xin

AU - Guan, Cha Xiang

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