Anti-Fibrotic and Anti-Inflammatory Role of NO-Sensitive Guanylyl Cyclase in Murine Lung

• Published in: International journal of molecular sciences Vol. 24; no. 14; p. 11661
• Main Authors: Englert, Nils, Burkard, Philipp, Aue, Annemarie, Rosenwald, Andreas, Nieswandt, Bernhard, Friebe, Andreas
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.07.2023; MDPI
• Subjects: Animals; Anti-inflammatory drugs; Cells; Collagen; Enzymes; Extracellular matrix; fibrosis; Growth factors; guanylyl cyclase; Health aspects; Immigration; Immune system; Inflammation; Investigations; lung; Lungs; Lymphocytes; Nitric oxide; Proteins; Pulmonary fibrosis; Smooth muscle; TGFβ; Transforming growth factors; Germany; lung; TGFβ; guanylyl cyclase; fibrosis; inflammation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms241411661

Pulmonary fibrosis is a chronic and progressive disease with limited therapeutic options. Nitric oxide (NO) is suggested to reduce the progression of pulmonary fibrosis via NO-sensitive guanylyl cyclase (NO-GC). The exact effects of NO-GC during pulmonary fibrosis are still elusive. Here, we used a NO-GC knockout mouse (GCKO) and examined fibrosis and inflammation after bleomycin treatment. Compared to wildtype (WT), GCKO mice showed an increased fibrotic reaction, as myofibroblast occurrence ( = 0.0007), collagen content ( = 0.0006), and mortality ( = 0.0009) were significantly increased. After fibrosis induction, lymphocyte accumulations were observed in the lungs of GCKO but not in WT littermates. In addition, the total number of immune cells, specifically lymphocytes ( = <0.0001) and neutrophils ( = 0.0047), were significantly higher in the bronchoalveolar lavage fluid (BALF) of GCKO animals compared to WT, indicating an increased inflammatory response in the absence of NO-GC. The pronounced fibrotic response in GCKO mice was paralleled by significantly increased levels of transforming growth factor β (TGFβ) in BALF ( = 0.0207), which correlated with the total number of immune cells. Taken together, our data show the effect of NO-GC deletion in the pathology of lung fibrosis and the effect on immune cells in BALF. In summary, our results show that NO-GC has anti-inflammatory and anti-fibrotic properties in the murine lung, very likely by attenuating TGFβ-mediated effects.