Open AccessAryl hydrocarbon receptor is essential for the pathogenesis of pulmonary arterial hypertension
Author(s) -
Masaki Tomita,
Makoto Okazawa,
Ryotaro Asano,
Takuya Inagaki,
Tatsuro Ishibashi,
Akiko Yamagishi,
Saori Umeki-Mizushima,
Motoi Nishimura,
Yusuke Manabe,
Hatsue IshibashiUeda,
Makoto Shirai,
Hirotsugu Tsuchimochi,
James T. Pearson,
Atsushi Kumanogoh,
Yasushi Sakata,
Takeshi Ogo,
Tadamitsu Kishimoto,
Yoshikazu Nakaoka
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2023899118
Subject(s) - pathogenesis , aryl hydrocarbon receptor , immune system , medicine , immunology , biomarker , cancer research , biology , transcription factor , biochemistry , gene
Significance Inflammatory signals are thought to be crucial for the pathogenesis of PAH; however, the underlying mechanism is still largely unknown. In this study, we demonstrate that AHR makes a causal contribution to the pathogenesis of PAH, activating a focal inflammatory response in the lungs and promoting infiltration of immune cells from the bone marrow. Furthermore, we found that PAH patients with higher AHR agonistic activity in sera are more susceptible to severe clinical events than those with lower activity. Because conventional therapy for pulmonary hypertension targeting pulmonary artery vasodilation has limited efficacy against severe PAH, the AHR-signaling pathway represents a promising therapeutic target for PAH. In addition, AHR agonistic activity in serum represents a biomarker for PAH.