Exosomes from Human Placenta Choriodecidual Membrane-Derived Mesenchymal Stem Cells Mitigate Endoplasmic Reticulum Stress, Inflammation, and Lung Injury in Lipopolysaccharide-Treated Obese Mice

• Published in: Antioxidants Vol. 11; no. 4; p. 615
• Main Authors: Chiang, Milton D, Chang, Chao-Yuan, Shih, Hung-Jen, Le, Van Long, Huang, Yen-Hua, Huang, Chun-Jen
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23.03.2022; MDPI
• Subjects: Apoptosis; Bacterial infections; CCAAT/enhancer-binding protein; Diet; DNA fragmentation; Endoplasmic reticulum; endoplasmic reticulum stress; Exosomes; High fat diet; Homeostasis; Hypoxia-inducible factors; IL-1β; Inflammation; Interleukin 6; Laboratory animals; Lipid peroxidation; Lipopolysaccharides; LPS; lung injury; Macrophages; Mesenchymal stem cells; Morphology; NF-κB protein; Obesity; Ostomy; Oxidation; Oxidative stress; Placenta; Proteins; Pyrin protein; Respiration; Sepsis; Stem cell transplantation; Stem cells; Tracheotomy; Tumor necrosis factor-α; Water content; United Kingdom > UK; United States > US; Taiwan; lung injury; exosomes; LPS; endoplasmic reticulum stress; obesity
• ISSN: 2076-3921; 2076-3921
• DOI: 10.3390/antiox11040615

Endoplasmic reticulum (ER) stress mediates the effects of obesity on aggravating sepsis-induced lung injury. We investigated whether exosomes from human placenta choriodecidual membrane-derived mesenchymal stem cells (pcMSCs) can mitigate pulmonary ER stress, lung injury, and the mechanisms of inflammation, oxidation, and apoptosis in lipopolysaccharide-treated obese mice. Diet-induced obese (DIO) mice (adult male C57BL/6J mice fed with a 12-week high-fat diet) received lipopolysaccharide (10 mg/kg, i.p.; DIOLPS group) or lipopolysaccharide plus exosomes (1 × 108 particles/mouse, i.p.; DIOLPSExo group). Our data demonstrated lower levels of ER stress (upregulation of glucose-regulated protein 78, phosphorylated eukaryotic initiation factor 2α, and C/EBP homologous protein; p = 0.038, <0.001, and <0.001, respectively), inflammation (activation of nuclear factor-kB, hypoxia-inducible factor-1α, macrophages, and NLR family pyrin domain containing 3; upregulation of tumor necrosis factor-α, interleukin-1β, and interleukin-6; p = 0.03, <0.001, <0.001, <0.001, <0.001, <0.001, and <0.001, respectively), lipid peroxidation (p < 0.001), and apoptosis (DNA fragmentation, p = 0.003) in lung tissues, as well as lower lung injury level (decreases in tidal volume, peak inspiratory flow, and end expiratory volume; increases in resistance, injury score, and tissue water content; p < 0.001, <0.001, <0.001, <0.001, <0.001, and =0.002, respectively) in the DIOLPSExo group than in the DIOLPS group. In conclusion, exosomes from human pcMSCs mitigate pulmonary ER stress, inflammation, oxidation, apoptosis, and lung injury in lipopolysaccharide-treated obese mice.