Bone marrow mesenchymal stem cells protect against bleomycin-induced pulmonary fibrosis in rat by activating Nrf2 signaling.
Pulmonary fibrosis is a progressive and lethal disorder. Although the precise mechanisms of pulmonary fibrosis are not fully understood, oxidant/antioxidant may play an important role in many of the processes of inflammation and fibrosis. Keap1-Nrf2-ARE pathway represents one of the most important cellular defense mechanisms against oxidative stress. Mesenchymal stem cells (MSC) are in clinical trials for widespread indications including musculoskeletal, neurological, cardiac and haematological disorders. One emerging concept is that MSCs may have paracrine, rather than a functional, roles in lung injury repair and regeneration. In the present study, we investigated bone marrow mesenchymal stem cells (BMSCs) for the treatment of bleomycin-induced pulmonary fibrosis. Our results showed that BMSCs administration significantly ameliorated the bleomycin mediated histological alterations and blocked collagen deposition with parallel reduction in the hydroxyproline level. The gene expression levels of
quinine oxidoreductase 1 (NQO1), gama-glutamylcysteine synthetase (γ-GCS), heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2), attenuated by bleomycin, were increased up to basal levels after BMSCs transplantation. BMSCs significantly increased superoxide dismutase (SOD) activity and inhibited malondialdehyde (MDA) production in the injured lung. The present study provides evidence that BMSCs may be a potential therapeutic reagent for the treatment of lung fibrosis.
Department of Hematology, Zhujiang Hospital, Southern Medical University Guangzhou, China ; Department of Pathophysiology, Wenzhou Medical University Wenzhou, Zhejiang Province, China.
Shirong
S
Ni
Department of Pediatrics, The Second Affiliated & Yuying Children's Hospital of Wenzhou Medical University Wenzhou, Zhejiang Province, China.
Dexuan
D
Wang
Department of Pathophysiology, Wenzhou Medical University Wenzhou, Zhejiang Province, China.
Xiaoxiao
X
Qiu
Teaching Center of Medical Functional Experiment, Wenzhou Medical University Wenzhou, Zhejiang Province, China.
Lingxia
L
Pang
Department of Pathophysiology, Wenzhou Medical University Wenzhou, Zhejiang Province, China.
Zhangjuan
Z
Song
Department of Hematology, Zhujiang Hospital, Southern Medical University Guangzhou, China.
Kunyuan
K
Guo
D000818:Animals; D001761:Bleomycin / Q000009:adverse effects; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D020011:Protective Agents / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000139:chemically induced; D051381:Rats; D015398:Signal Transduction
D051267:NF-E2-Related Factor 2; D020011:Protective Agents; D001761:Bleomycin; D008315:Malondialdehyde; D003094:Collagen; D006909:Hydroxyproline
BMSCs; Nrf2; Pulmonary fibrosis; antioxidant enzymes; oxidative stress