RT Journal Article SR Electronic T1 A selective glucocorticoid receptor modulator attenuates lung inflammation and improves alveolarization in a neonatal rat model of bronchopulmonary dysplasia JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.04.28.441723 DO 10.1101/2021.04.28.441723 A1 Shoichi Ishikawa A1 Tohru Ogihara A1 Shigeo Yamaoka A1 Jun Shinohara A1 Shigeru Kawabata A1 Yoshinobu Hirose A1 Akira Ashida YR 2021 UL http://biorxiv.org/content/early/2021/04/28/2021.04.28.441723.abstract AB Background Bronchopulmonary dysplasia (BPD) is a major problem for extremely preterm infants. Glucocorticoids effectively treat BPD; however, they have many side effects. Compound A (Cpd A) is a nonsteroidal Selective Glucocorticoid Receptor Modulator (SEGRM) that acts as a glucocorticoid receptor ligand without inducing the expression of glucocorticoid-response element-driven genes. Cpd A reportedly has anti-inflammatory properties with fewer side effects than glucocorticoids.Methods Using a bleomycin (Bleo)-induced BPD model, we evaluated the therapeutic effects of Cpd A. 0-day-old Sprague-Dawley rats were administered Bleo for 10 days and treated with dexamethasone (Dex) or Cpd A from day 0 to 13. We evaluated lung pathology by histology and the mRNA levels of interleukin (IL)-1β, transforming growth factor (TGF)-β1 and chemokines, CXCL1 and CCL2.Results Bleo-treated mice had lungs with impaired alveolarization. Dex and Cpd A treatments improved the alveolar structure, attenuating the lung injury. Bleo-exposed lungs had increased inflammatory cells recruitment and inflammatory mediator mRNA levels. Cpd A treatment reduced inflammatory cells infiltration and CXCL1, CCL2 and TGF-β1 expression.Conclusion Cpd A improved lung inflammation and alveolar maturation arrest, and restored histological and biochemical changes in a model of BPD. SEGRMs, including Cpd A, are promising candidates for the therapy of BPD.Impact Statement○ What is the key message of your article?Compound A decreased lung inflammation and improved lung morphometric changes in Bleomycin-exposed lungs.○ What does it add to the existing literature?Compound A has anti-inflammatory effects in an experimental model of BPD.○ What is the impact?SEGRMs, including Cpd A, may be promising candidates for the therapy of BPD.Competing Interest StatementThe authors have declared no competing interest.