Transcriptome analysis of bleomycin-induced pulmonary fibrosis in transgenic mice with modifying p38 signal in the lungs: exploration of the novel therapeutic targets for idiopathic pulmonary fibrosis

DOI Web Site
  • Shuichi Matsuda
    Dept. Biomed. Sci., Grad. Sch. Med., Chiba Univ. Dept. Respirology, Grad. Sch. Med., Chiba Univ.
  • Kim Jundal
    Life Sci. Ctr. for Survival Dynamics, Tsukuba Adv. Res. Alliance, Tsukuba Univ.
  • Sugiyama Fumihiro
    Lab. Anim. Resour. Ctr. & Trans-Border Med. Res. Ctr., Tsukuba Univ.
  • Matsuo Yuji
    Dept. Respirology, Grad. Sch. Med., Chiba Univ.
  • Ishida Junji
    Life Sci. Ctr. for Survival Dynamics, Tsukuba Adv. Res. Alliance, Tsukuba Univ.
  • Murata Kazuya
    Life Sci. Ctr. for Survival Dynamics, Tsukuba Adv. Res. Alliance, Tsukuba Univ. Lab. Anim. Resour. Ctr. & Trans-Border Med. Res. Ctr., Tsukuba Univ.
  • Nakamura Kanako
    Grad. Sch. Sci. & Tech., Tsukuba Univ.
  • Namiki Kana
    Dept. Biochem. & Mol. Pharmacol., Grad. Sch. Med., Chiba Univ.
  • Sudo Tatsuhiko
    Chem. Biol. Core Facility & Antibiotics Lab., RIKEN Adv. Sci. Inst.
  • Kuwaki Tomoyuki
    Dept. Physiol., Grad. Sch. Med. & Dent. Sci., Kagoshima Univ
  • Hatano Masahiko
    Dept. Biomed. Sci., Grad. Sch. Med., Chiba Univ.
  • Tatsumi Koichiro
    Dept. Respirology, Grad. Sch. Med., Chiba Univ.
  • Fukamizu Akiyoshi
    Life Sci. Ctr. for Survival Dynamics, Tsukuba Adv. Res. Alliance, Tsukuba Univ.
  • Kasuya Yoshitoshi
    Dept. Biomed. Sci., Grad. Sch. Med., Chiba Univ. Dept. Biochem. & Mol. Pharmacol., Grad. Sch. Med., Chiba Univ.

Bibliographic Information

Other Title
  • 肺p38シグナル遺伝子改変マウスのブレオマイシン誘導肺線維症に関するトランスクリプトーム解析：特発性肺線維症の新規治療標的の探索

Abstract

<p>p38 mitogen-activated protein kinase (MAPK) may contribute to the development of idiopathic pulmonary fibrosis (IPF) through its activation in alveolar epithelial type II cells (AEC II) in response to environmental stresses. We examined whether AEC II-specific　genetically modified p38 activity causes worsening of bleomycin (BLM)-induced pulmonary fibrosis and investigated the potential therapeutic targets for IPF progression by assessing its transcriptome. The three mouse genotypes having different p38 activity in AEC II, MKK6-constitutive active, wild type, and p38-dominant negative, received intratracheal administration of BLM and the lungs were analyzed at 8 days post-instillation, known as an active fibrosis phase. Increased histopathological severity, reduced compliance, and higher collagen content of the lungs correlated with increased p38 activity in AEC II. Transcriptome analysis of them revealed that the differentially expressed genes, upregulated by BLM and associated with upregulation of p38 MAPK pathway, were enriched for functions related to endoplasmic reticulum, extracellular matrix, and immune system. Comparison of our data with a publicly available IPF data determined the target genes involved in IPF progression. These findings indicate that p38 MAPK in AEC II plays an important role in IPF progression.</p>

Journal

Keywords

Details 詳細情報について

Report a problem

Back to top