Naftopidil reduced the proliferation of lung fibroblasts and bleomycin-induced lung fibrosis in mice.
Hirokazu UrushiyamaYasuhiro TerasakiShinya NagasakaNariaki KokuhoYouko EndoMika TerasakiShinobu KunugiKosuke MakitaHideaki IsagoKeisuke HosokiKunihiko SoumaTakashi IshiiHirotaka MatsuzakiYoshihisa HiraishiYu MikamiSatoshi NoguchiHiroyuki TamiyaAkihisa MitaniYasuhiro YamauchiAkira ShimizuTakahide NagasePublished in: Journal of cellular and molecular medicine (2019)
Naftopidil, an α-1 adrenoceptor antagonist with few adverse effects, is prescribed for prostate hyperplasia. Naftopidil inhibits prostate fibroblast proliferation; however, its effects on lung fibroblasts and fibrosis remain largely unknown. Two normal and one idiopathic pulmonary fibrosis human lung fibroblast lines were cultured with various naftopidil concentrations with or without phenoxybenzamine, an irreversible α-1 adrenoceptor inhibitor. We examined the incorporation of 5-bromo-2'-deoxyuridine into DNA and lactic acid dehydrogenase release by enzyme-linked immunosorbent assay, cell cycle analysis by flow cytometry, scratch wound-healing assay, and mRNA expressions of type IV collagen and α-smooth muscle actin by polymerase chain reaction. Effects of naftopidil on bleomycin-induced lung fibrosis in mice were evaluated using histology, micro-computed tomography, and surfactant protein-D levels in serum. Naftopidil, dose-dependently but independently of phenoxybenzamine, inhibited 5-bromo-2'-deoxyuridine incorporation in lung fibroblasts. Naftopidil induced G1 cell cycle arrest, but lactic acid dehydrogenase release and migration ability of lung fibroblasts were unaffected. Naftopidil decreased mRNA expressions of type IV collagen and α-smooth muscle actin in one normal lung fibroblast line. Histological and micro-computed tomography examination revealed that naftopidil attenuated lung fibrosis and decreased serum surfactant protein-D levels in bleomycin-induced lung fibrosis in mice. In conclusion, naftopidil may have therapeutic effects on lung fibrosis.
Keyphrases
- computed tomography
- smooth muscle
- cell cycle
- wound healing
- idiopathic pulmonary fibrosis
- prostate cancer
- high glucose
- lactic acid
- diabetic rats
- magnetic resonance imaging
- magnetic resonance
- flow cytometry
- type diabetes
- endothelial cells
- drug induced
- cell death
- metabolic syndrome
- positron emission tomography
- amino acid
- oxidative stress
- pet ct
- single cell
- benign prostatic hyperplasia
- image quality