Details

Autor(en) / Beteiligte

• Hao, Mengyao
• Fu, Rong
• Tai, Jun
• Tian, Zhenhuan
• Yuan, Xia
• Chen, Yang
• Wang, Mingjin
• Jiang, Huimin
• Ji, Ming
• Lai, Fangfang
• Xue, Nina
• Bai, Liping
• Zhu, Yizhun
• Lv, Xiaoxi
• Chen, Xiaoguang
• Jin, Jing

Titel

S1PR1 serves as a viable drug target against pulmonary fibrosis by increasing the integrity of the endothelial barrier of the lung

Ist Teil von

• Acta pharmaceutica Sinica. B, 2023-03, Vol.13 (3), p.1110-1127

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2023

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2–3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy. Activation of S1PR1 with IMMH002 elicits a potent therapeutic effect in bleomycin-induced fibrosis by increasing tight junctions in endothelial cells and protecting the integrity of endothelial barrier. [Display omitted]