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Role of Bronchopulmonary C‐fibers in Bleomycin‐induced Rapid Shallow Breathing (RSB) and Idiopathic Pulmonary Fibrosis (IPF) in Mice
Author(s) -
Wei Wan,
Zhuang Jianguo,
Gao Xiuping,
Jiao Yang,
Xu Fadi
Publication year - 2020
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.2020.34.s1.04540
Subject(s) - medicine , bleomycin , lung , idiopathic pulmonary fibrosis , pulmonary fibrosis , hypoxemia , inflammation , pathology , pathogenesis , fibrosis , hydroxyproline , immunology , chemotherapy
IPF is characterized by an irreversible loss of lung function associated with RSB, dyspnea, and hypoxemia, which often leads to death within 3–5 years due to respiratory failure. Inflammation and abnormal wound healing of the interstitial and alveolar spaces in the lungs with excessive proliferation of myofibroblasts (over‐secretion/expression of collagens and α‐smooth muscle actin, α‐SMA) result in fibrosis. Substance P (SP) is known to participate in fibrosis in multiple organs, such as cardiac, renal and liver fibrosis, and wound healing process, but its role in pathogenesis of IPF is unexplored. Because inflammation mediators could stimulate bronchopulmonary C‐fibers (PCFs) to release SP (the major source of inflammatory SP releasing in the lungs) and evoke neurogenic inflammation and RSB (dyspnea), here we asked whether PCFs and neurogenic SP would involve in the pathogenesis of IPF. To this end, four groups of mice pretreated with neonatal capsaicin (for PCF degeneration) or its vehicle received endotracheally (by transoral route) saline (Ctrl) or bleomycin (BLM) respectively. On the 21 st day post pretreatment, ventilation, heart rate, and SpO 2 were measured. After subsequent euthanasia, BALF and the right lung tissues were collected to detect inflammatory cells, SP, and hydroxyproline, while the left lungs were fixed for histological assessment of IPF, pulmonary inflammation, and α‐SMA immunoreactivity. The results showed that in PCF intact mice, BLM induced RSB, hypoxemia, IPF (upregulation of pulmonary SP, α‐SMA, and hydroxyproline), and pulmonary inflammation. PCF degeneration: 1) eliminated the BLM‐induced RSB and SP upregulation; 2) failed to affect the BLM‐induced hypoxemia; and 3) aggravated IPF (upregulation of α‐SMA and hydroxyproline) and pulmonary inflammation. Our results suggest that PCFs are responsible for the BLM‐induced RSB. On the other hand, PCFs, likely via releasing SP, are protective for the lungs from genesis of IPF through suppressing pulmonary inflammation, α‐SMA and hydroxyproline.