Related Experiment Video
Updated: Mar 25, 2026
Refined Murine Model of Idiopathic Pulmonary Fibrosis
Published on: June 17, 2025
Exercise Reduces Lung Fibrosis Involving Serotonin/Akt Signaling
Paulo Rogerio Pereira1, Manoel Carneiro Oliveira-Junior, Breanne Mackenzie
11Laboratory of Pulmonary and Exercise Immunology, Nove de Julho University, São Paulo, BRAZIL; 2Laboratory of Experimental Therapeutics, School of Medicine, University of São Paulo, São Paulo, BRAZIL; 3COPD and Asthma Research Group, Department of Pneumology, University Hospital Freiburg, Freiburg, GERMANY; 4Laboratory of Cellular Biology, School of Medicine, University of Sao Paulo, São Paulo, BRAZIL; 5Comprehensive Pneumology Centre, University Hospital of the Ludwig Maximilians University Munich, Munich, GERMANY; 6Laboratory of Immunopharmacology, Institute Oswaldo Cruz, Oswaldo Cruz Foundation, Rio de Janeiro, BRAZIL; and 7Laboratory of Experimental Air Pollution, Department of Pathology, School of Medicine, University of Sao Paulo, São Paulo, BRAZIL.
Purpose:
Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia, which involves aberrant serotonin (5-hydroxytryptamine [5-HT]) and Akt signaling. As protective effects of chronic aerobic training (AT) have been demonstrated in the context of lung injury, this study investigated whether AT attenuates bleomycin-induced lung fibrosis partly via a reduction of 5-HT and AKT signaling.
Methods:
Seventy-two C57BL/6 male mice were distributed in Control (Co), Exercise (Ex), Fibrosis (Fi), and Fibrosis + Exercise (Fi + Ex) groups. Bleomycin (1.5 UI·kg) was administered on day 1 and treadmill AT began on day 15 and continued for 60 min·d, 5 d·wk for 4 wk. We evaluated total and differential cell counts in bronchoalveolar lavage (BAL), interleukin (IL)-1β, IL-6, CXCL1/KC, IL-10, tumor necrosis factor α, and transforming growth factor β levels in BAL, collagen content in lung parenchyma, 5-HT levels in BAL fluid and in serum, the expression of 5-HT2B receptor, and Akt phosphorylation in lung tissue.
Results:
AT reduced bleomycin-increased number of total cells (P < 0.001), neutrophils (P < 0.01), macrophages (P < 0.01), and lymphocytes (P < 0.05) in BAL. It also reduced the levels of IL-1β (P < 0.01), IL-6 (P < 0.05), CXCL1/KC (P < 0.001), tumor necrosis factor α (P < 0.001), and transforming growth factor β (P < 0.001). It increased expression of ant-inflammatory cytokine IL-10 (P < 0.001). It reduced bleomycin-increased 5-HT levels in BAL (P < 0.001) and in serum (P < 0.05). Reductions in collagen fiber deposition (P < 0.01), 5-HT2B receptor expression (P < 0.01), and Akt phosphorylation in lung tissue were observed.
Conclusions:
AT accelerates the resolution of lung inflammation and fibrosis in a model of bleomycin-induced lung fibrosis partly via attenuation of 5-HT/Akt signaling.
