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Cyp19a1 is essential for macrophage function and pulmonary tissue repair following airway epithelial injury
Author(s) -
Han Weiguo,
Yang Weizhu,
Kovalchuk Nataliia,
Ding Liang,
Liu Pengfei,
Zhang QingYu,
Van Winkle Laura,
Ding Xinxin
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.03063
Subject(s) - andrology , biology , epithelium , respiratory epithelium , macrophage , lung , alveolar macrophage , cell type , microbiology and biotechnology , immunology , cell , pathology , medicine , in vitro , biochemistry
CYP19A1 (the aromatase) is a key enzyme in the biosynthesis of estrogens, which have important regulatory functions, including roles as a major mitogenic stimulus for cellular proliferation. Using a new myeloid cell‐specific Cyp19a1 ‐null ( Cyp19a1 ‐null) mouse model, we tested the role of macrophage CYP19A1 in pulmonary regenerative response to naphthalene‐induced bronchiolar epithelial cell injury. Wild‐type and Cyp19a1 ‐null mice were treated with naphthalene (200 mg/kg, IP) to induce acute lung injury, or with corn oil as a vehicle control. Mouse lung was examined at 24 hour, 72 hours, or 14 days after the treatment, for extent of acute airway injury, post‐injury cellular proliferation, and tissue repair, respectively. At 24 hours, a genotype difference in the extent of naphthalene‐induced airway injury was not detected. At 72 hours, the fraction of airway epithelial cells that are positive for the cell proliferation marker Ki67 was higher in naphthalene‐treated wild‐type mice (40%‐70%) than in naphthalene‐treated Cyp19a1 ‐null mice (20‐30%); whereas the fraction was much lower in corn oil treated control mice (3‐5%). At 14 days, the bronchiolar epithelium was recovered to a greater extent in wild‐type (~80%) than in the Cyp19a1 ‐null mice (<30%), as indicated by the abundance of Club cells (positive for Club cell secretary protein) in the airway epithelium. Further studies of isolated macrophages indicated that Cyp19a1 ‐null macrophages had reduced phagocytosis (by ~70%) and migration (by ~50%) activities, compared to wild‐type controls. Thus, the loss of macrophage CYP19A1negativelyimpacted macrophage function and impeded the post‐injury cellular proliferation and tissue repair in the lung airways.