The effects of aerosolized STAT1 antisense oligodeoxynucleotides on rat pulmonary fibrosis.
Previous study showed that aerosolized signal transducer and activator of transcription-1 (STAT1) antisense oligodeoxynucleotide (ASON) inhibited the expression of STAT1 and ICAM-1 mRNA and protein in alveolar macrophages (AMs) and decreased the concentrations of TGF-beta, PDGF and TNF-alpha in bronchioalveolar lavage fluid (BALF) in bleomycin (BLM)-induced rat pulmonary fibrosis. Administration of STAT1 ASON ameliorated alveolitis in rat pulmonary fibrosis. However, further investigations are needed to determine whether there is an effect from administration of STAT1 ASON on fibrosis. This study investigated the effect of aerosolized STAT1 ASON on the expressions of inflammatory mediators, hydroxyproline and type I and type III collagen mRNA in BLM-induced rat pulmonary fibrosis. The results showed that STAT1 ASON applied by aerosolization could ameliorate alveolitis and fibrosis, inhibit the expressions of inflammatory mediators, decrease the content of hydroxyproline, and suppress the expressions of type I and type III collagen mRNA in lung tissue in BLM-induced rat pulmonary fibrosis. These results suggest that aerosolized STAT1 ASON might be considered as a promising new strategy in the treatment of pulmonary fibrosis.
Wang
Wen Jun
WJ
The Department of Respiratory Medicine, Affiliated Hospital of Luzhou Medical College, Luzhou 646000, China.
Liao
Bin
B
Zeng
Ming
M
Zhu
Chen
C
Fan
Xian Ming
XM
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D001761:Bleomycin / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D008081:Liposomes / Q000494:pharmacology; D008168:Lung / Q000473:pathology; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D050794:STAT1 Transcription Factor / Q000037:antagonists & inhibitors* / Q000235:genetics; D051901:Smad4 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000336:Aerosols; D024042:Collagen Type I; D024061:Collagen Type III; D008081:Liposomes; D020319:Oligodeoxyribonucleotides, Antisense; D010982:Platelet-Derived Growth Factor; D050794:STAT1 Transcription Factor; D051901:Smad4 Protein; C490811:Smad4 protein, rat; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C075278:platelet-derived growth factor A; D001761:Bleomycin; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma