Vagotomy attenuates bleomycin-induced pulmonary fibrosis in mice.
The progression of pulmonary fibrosis (PF) entails a complex network of interactions between multiple classes of molecules and cells, which are closely related to the vagus nerve. Stimulation of the vagus nerve increases fibrogenic cytokines in humans, therefore, activation of the nerve may promote PF. The hypothesis was tested by comparing the extent and severity of fibrosis in lungs with and without vagal innervation in unilaterally vagotomized mice. The results show that in vagotomized lungs, there were less collagen staining, less severe fibrotic foci (subpleural, peri-vascular and peri-bronchiolar lesions) and destruction of alveolar architecture; decreased collagen deposition (denervated vs intact: COL1α1, 19.1 ± 2.2 vs 22.0 ± 2.6 ng/mg protein; COL1α2, 4.5 ± 0.3 vs 5.7 ± 0.5 ng/mg protein; p < 0.01, n = 21) and protein levels of transforming growth factor beta and interleukin 4; and fewer myofibroblast infiltration (denervated vs intact: 1.2 ± 0.2 vs 3.2 ± 0.6 cells/visual field; p < 0.05, n = 6) and M2 macrophages [though the infiltration of macrophages was increased (denervated vs intact: 112 ± 8 vs 76 ± 9 cells/visual field; p < 0.01, n = 6), the percentage of M2 macrophages was decreased (denervated vs intact: 31 ± 4 vs 57 ± 9%; p < 0.05, n = 5)]. It indicated that the vagus nerve may influence PF by enhancing fibrogenic factors and fibrogenic cells.
Robley Rex VA Medical Center, Louisville, KY, USA.|Division of Pulmonary, Critical Care and Sleep Disorders, Department of Medicine, University of Louisville, Louisville, KY, USA.
Nana
N
Song
Robley Rex VA Medical Center, Louisville, KY, USA.|Division of Pulmonary, Critical Care and Sleep Disorders, Department of Medicine, University of Louisville, Louisville, KY, USA.
Jun
J
Liu
Robley Rex VA Medical Center, Louisville, KY, USA.
Saad
S
Shaheen
Division of Pulmonary, Critical Care and Sleep Disorders, Department of Medicine, University of Louisville, Louisville, KY, USA.
Lei
L
Du
Robley Rex VA Medical Center, Louisville, KY, USA.
Mary
M
Proctor
Robley Rex VA Medical Center, Louisville, KY, USA.|Division of Pulmonary, Critical Care and Sleep Disorders, Department of Medicine, University of Louisville, Louisville, KY, USA.|Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, USA.
Jesse
J
Roman
Robley Rex VA Medical Center, Louisville, KY, USA.|Division of Pulmonary, Critical Care and Sleep Disorders, Department of Medicine, University of Louisville, Louisville, KY, USA.|Department of Physiology and Biophysics, University of Louisville, Louisville, KY, USA.
Jerry
J
Yu
D000818:Animals; D001761:Bleomycin; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002454:Cell Differentiation; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000473:pathology; D008264:Macrophages / Q000378:metabolism; D008810:Mice, Inbred C57BL; D058628:Myofibroblasts / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000473:pathology / Q000628:therapy*; D014628:Vagotomy
D016207:Cytokines; D001761:Bleomycin; D003094:Collagen