Prostaglandin F receptor signaling facilitates bleomycin-induced pulmonary fibrosis independently of transforming growth factor-Β

Toru Oga, Toshiyuki Matsuoka, Chengcan Yao, Kimiko Nonomura, Shiho Kitaoka, Daiji Sakata, Yoshihiro Kita, Kiminobu Tanizawa, Yoshio Taguchi, Kazuo Chin, Michiaki Mishima, Takao Shimizu, Shuh Narumiya

研究成果: ジャーナルへの寄稿学術誌査読

146 被引用数 (Scopus)


Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by fibroblast proliferation and excess deposition of collagen and other extracellular matrix (ECM) proteins, which lead to distorted lung architecture and function. Given that anti-inflammatory or immunosuppressive therapy currently used for IPF does not improve disease progression therapies targeted to blocking the mechanisms of fibrogenesis are needed. Although transforming growth factor-Β (TGF-Β) functions are crucial in fibrosis, antagonizing this pathway in bleomycin-induced pulmonary fibrosis, an animal model of IPF, does not prevent fibrosis completely, indicating an additional pathway also has a key role in fibrogenesis. Given that the loss of cytosolic phospholipase A 2 (cPLA 2) suppresses bleomycin-induced pulmonary fibrosis, we examined the roles of prostaglandins using mice lacking each prostoaglandin receptor. Here we show that loss of prostaglandin F (PGF) receptor (FP) selectively attenuates pulmonary fibrosis while maintaining similar levels of alveolar inflammation and TGF-Β stimulation as compared to wild-type (WT) mice, and that FP deficiency and inhibition of TGF-Β signaling additively decrease fibrosis. Furthermore, PGF 2α is abundant in bronchoalveolar lavage fluid (BALF) of subjects with IPF and stimulates proliferation and collagen production of lung fibroblasts via FP, independently of TGF-Β. These findings show that PGF 2α-FP signaling facilitates pulmonary fibrosis independently of TGF-Β and suggests this signaling pathway as a therapeutic target for IPF.

ジャーナルNature medicine
出版ステータス出版済み - 12月 2009

!!!All Science Journal Classification (ASJC) codes

  • 生化学、遺伝学、分子生物学(全般)


「Prostaglandin F receptor signaling facilitates bleomycin-induced pulmonary fibrosis independently of transforming growth factor-Β」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。