연구성과 홍보

Biomed Pharmacother 2023 Dec:168:115647.

Title : Superoxide dismutase secreting Bacillus amyloliquefaciens spores attenuate pulmonary fibrosis

Authors : Na Hyun Kim1, Hee Young Kim2, Jang Ho Lee1, Inik Chang3, Sun-Hee Heo1, Jiseon Kim4, Jeong Hyun Kim5, Jung-Hyun Kang5, Sei Won Lee6*

Affiliations :

1Department of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

2Department of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; BiomLogic, Inc., Seoul, Republic of Korea.

3BiomLogic, Inc., Seoul, Republic of Korea.

4Department of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Department of Pharmacology and Regnerative Medicine, University of Illinois College of Medicine, Chicago, USA.

5GenoFocus, Inc., Daejeon, Republic of Korea.

6Department of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

DOI : 10.1016/j.biopha.2023.115647.

Abstract :

Superoxide dismutase (SOD) can convert active oxygen to oxygen or hydrogen peroxide, and recent research has suggested that it can protect against lung damage and fibrosis. Clinical applications based on SOD remain limited however due to costs and low stability. We here investigated a potential new therapeutic delivery system for this enzyme in the form of SOD-overexpressing Bacillus amyloliquefaciens spores which we introduced into a bleomycin-induced pulmonary fibrosis mouse model. This treatment significantly alleviated the disease, as quantified using a hydroxyproline assay, at 107 colony forming unit (CFU) of Bacillus spores per day. Exposure of the mice to the spores was further found to decrease the lung mRNA levels of CTGF, Col1a1, α-SMA, TGF-β, TNF-α, and IL-6, and the protein levels of TGF-β, Smad2/3, αSMA and Col1a1, all major indicators of pulmonary fibrosis. Survival benefits, and reduced byproducts of lipid peroxidase such as malondialdehyde and 4-hydroxynen, were also noted in the treated animals. The beneficial effects of these Bacillus spores on pulmonary fibrosis were further found to be greater than the equivalent free SOD concentration. Immunofluorescence staining of primary pulmonary fibroblasts extracted from the bleomycin-induced model showed decreased αSMA expression following the in vivo treatment with SOD-overexpressing Bacillus. Our treatment approach SOD through Bacillus spores shows beneficial effects against pulmonary fibrosis, combined with the suppression of the SMAD/TGF-β pathway, suggesting that it is an effective novel delivery route for antioxidants.