| First Author | Okamoto T | Year | 2022 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 323 |
| Issue | 3 | Pages | L329-L337 |
| PubMed ID | 35881171 | Mgi Jnum | J:330034 |
| Mgi Id | MGI:7355173 | Doi | 10.1152/ajplung.00061.2022 |
| Citation | Okamoto T, et al. (2022) Muc5b plays a role in the development of inflammation and fibrosis in hypersensitivity pneumonitis induced by Saccharopolyspora rectivirgula. Am J Physiol Lung Cell Mol Physiol 323(3):L329-L337 |
| abstractText | Previously we have shown that a gain-of-function MUC5B promoter variant (rs35705950) is the strongest risk factor for the development of idiopathic pulmonary fibrosis. We have also found that Muc5b overexpression reduces mucociliary clearance in mice, potentially leading to recurrent injury to the bronchoalveolar epithelia. Hypersensitivity pneumonitis (HP) is induced by inhalation of numerous causative antigens that may be affected by mucociliary clearance. We conducted this study to determine the role of Muc5b in a mouse model of HP induced by Saccharopolyspora rectivirgula (SR) antigen. We used Muc5b-deficient and wild-type (WT) mice to determine whether Muc5b plays a role in inflammation and fibrosis at 3 and 6 wk in an SR model of HP. We measured cell concentrations and MUC5B expression in whole lung lavage (WLL) and quantified fibrosis using hydroxyproline assay and second harmonic generation. Muc5b expression in WLL fluid was significantly increased in SR-exposed WT mice compared with saline controls. WT mice challenged with SR developed more inflammation and lung fibrosis at 6 wk compared with 3 wk postexposure. Moreover, we found that 6 wk following challenge with SR, Muc5b-deficient mice had less lung inflammation and less lung fibrosis than Muc5b WT mice. Furthermore, Muc5b-deficient mice had significantly lower concentrations of TGF-beta1 in the WLL compared with Muc5b WT mice at 6 wk of exposure. Muc5b appears to play a role in fibrosis in the animal model of HP and this may have implications for HP in humans. |
