Induced Pluripotent Stem Cells Attenuate Acute Lung Injury Induced by Ischemia Reperfusion via Suppressing the High Mobility Group Box-1
Yijun Li,
Shun Wang,
Jinbo Liu,
Xingyu Li,
Meng Lu,
Xiaokai Wang,
Yansong Ren,
Xiaoming Li,
Meng Xiang
Affiliations
Yijun Li
Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, People’s Republic of China
Shun Wang
Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, People’s Republic of China
Jinbo Liu
Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, People’s Republic of China
Xingyu Li
Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, People’s Republic of China
Meng Lu
Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, People’s Republic of China
Xiaokai Wang
Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, People’s Republic of China
Yansong Ren
Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, People’s Republic of China
Xiaoming Li
Department of Pathology, People’s Hospital of Bao’an District, Affiliated Bao’an Hospital of Shenzhen, Southern Medical University, The Second Affiliated Hospital of Shenzhen University, Shenzhen, People’s Republic of China
Meng Xiang
Department of Physiology & Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, People’s Republic of China
Pulmonary endothelial cell injury is a hallmark of acute lung injury. High-mobility group box 1 (HMGB1) can modulate the inflammatory response via endothelial cell activation and release of inflammatory molecules. Thus, we tested whether induced pluripotent stem cells (iPSCs) can alleviate ischemia/reperfusion (I/R) induced lung injury, and, if so, whether HMGB1 mediates the effect in a male C57BL/6 mouse model. Intravenously injected iPSCs into mice 2 h after I/R showed a significant attenuation of lung injury (assessed by lung mechanics, edema, and histology) 24 h after reperfusion (compared with controls), along with decreases in HMGB1, phosphorylated nuclear factor-κB, inflammatory cytokines [interleukin (IL)1β, IL6 and tumor necrosis factor-α], and the activation of endothelial cells. Furthermore, these effects of iPSCs can be mimicked by blocking HMGB1 with an inhibitor in vivo and in vitro. We conclude that iPSCs can be a potential therapy for I/R-induced lung injury. These cells may exert therapeutic effects through blocking HMGB1 and inflammatory cytokines.
