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α7 nicotinic acetylcholine receptor (α7 nAChR, coded by Chrna7 ) is indispensible in dampening proinflammatory responses. However, whether α7 nAChR would play a role in regulating bleomycin (BLM)-induced lung fibrosis is less investigated. Here, we intratracheally challenged wildtype and Chrna7  -/- mice with BLM to elicit lung fibrosis. Taken advantage of this model, we measured body weight loss, lung fibrogenic genes ( Acta2 , Col1a1 , Fsp1 , and Fstl1 ), histology, Masson's trichrome staining, hydroxyproline levels, and expression of α-SMA at protein levels in the BLM-challenged lung for evaluating severity of lung fibrosis. We also pretreated human fibroblasts (MRC5 cell line) and isolated mouse lung fibroblasts with GTS-21 (an α7 nAChR agonist) to study its effects on TGF-β-stimulated profibrotic profiles. We found that lung Chrna7 expression and CD4 + CHAT + (Choline acetyltransferase, an enzyme for local acetylcholine synthesis) cells were 12-fold and 4.5-fold respectively elevated in the early stage of lung fibrosis. Deletion of Chrna7 prevented body weight loss and reduced lung fibrogenic genes ( Acta2 , Col1a1 , Fsp1 , and Fstl1 ) and Arg 1 (coding arginase 1). Deletion of Chrna7 attenuated lung arginase 1 + Ly6C + cells, Masson's trichrome staining, hydroxyproline levels, and expression of α-SMA at protein levels in BLM-challenged mice. Mechanistically, activation of α7 nAChR in human fibroblasts increased TGF-β-induced phosphorylation of Smad2/3 and transcription of fibrogenic genes ( Acta2 , Col1a1 ). In isolated mouse lung fibroblasts, activation of α7 nAChR also enhanced TGF-β induced-transcription of fibrogenic genes; however, deletion of Chrna7 diminished these effects. Taken together, deficiency of α7 nAChR could suppress the development of BLM-induced lung fibrosis. Thus, α7 nAChR might be a novel therapeutic target for treating lung fibrosis.

Deficiency of α7 Nicotinic Acetylcholine Receptor Attenuates Bleomycin-Induced Lung Fibrosis in Mice