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Let-7i-5p Mediates the Therapeutic Effects of Exosomes from Human Placenta Choriodecidual Membrane-Derived Mesenchymal Stem Cells on Mitigating Endotoxin-Induced Mortality and Liver Injury in High-Fat Diet-Induced Obese Mice.

ABSTRACT: Obesity complicates sepsis and increases the mortality of sepsis. We examined the effects of exosomes (from human placenta choriodecidual membrane-derived mesenchymal stem cells, pcMSCs) on preventing sepsis in obesity and the mitigating role of hsa-let-7i-5p microRNA. Obese mice (adult male C57BL/6J mice fed a high-fat diet for 12 weeks) received normal saline (HFD), endotoxin (10 mg/kg, intraperitoneal (ip); HFDLPS), endotoxin with exosomes (1 × 108 particles/mouse, ip; HLE), or endotoxin with let-7i-5p microRNA inhibitor-pretreated exosomes (1 × 108 particles/mouse, ip; HLEi). Our data demonstrated that the 48-h survival rate in the HLE (100%) group was significantly higher than in the HFDLPS (50%) and HLEi (58.3%) groups (both p < 0.05). In the surviving mice, by contrast, levels of liver injury (injury score, plasma aspartate transaminase and alanine transaminase concentrations, tissue water content, and leukocyte infiltration in liver tissues; all p < 0.05), inflammation (nuclear factor-κB activation, hypoxia-inducible factor-1α activation, macrophage activation, and concentrations of tumor necrosis factor-α, interleukin-6, and leptin in liver tissues; all p < 0.05), and oxidation (malondialdehyde in liver tissues, with p < 0.001) in the HLE group were significantly lower than in the HFDLPS group. Levels of mitochondrial injury/dysfunction and apoptosis in liver tissues in the HLE group were also significantly lower than in the HFDLPS group (all p < 0.05). Inhibition of let-7i-5p microRNA offset the effects of the exosomes, with most of the aforementioned measurements in the HLEi group being significantly higher than in the HLE group (all p < 0.05). In conclusion, exosomes mitigated endotoxin-induced mortality and liver injury in obese mice, and these effects were mediated by let-7i-5p microRNA.

SUBMITTER: Chang CY

PROVIDER: S-EPMC8779189 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Let-7i-5p Mediates the Therapeutic Effects of Exosomes from Human Placenta Choriodecidual Membrane-Derived Mesenchymal Stem Cells on Mitigating Endotoxin-Induced Mortality and Liver Injury in High-Fat Diet-Induced Obese Mice.

Chang Chao-Yuan CY Chen Kung-Yen KY Shih Hung-Jen HJ Chiang Milton M Huang I-Tao IT Huang Yen-Hua YH Huang Chun-Jen CJ

Pharmaceuticals (Basel, Switzerland) 20211227 1

Obesity complicates sepsis and increases the mortality of sepsis. We examined the effects of exosomes (from human placenta choriodecidual membrane-derived mesenchymal stem cells, pcMSCs) on preventing sepsis in obesity and the mitigating role of hsa-let-7i-5p microRNA. Obese mice (adult male C57BL/6J mice fed a high-fat diet for 12 weeks) received normal saline (HFD), endotoxin (10 mg/kg, intraperitoneal (ip); HFDLPS), endotoxin with exosomes (1 × 10<sup>8</sup> particles/mouse, ip; HLE), or end ...[more]

PMID: 35056093

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Dataset Information

Let-7i-5p Mediates the Therapeutic Effects of Exosomes from Human Placenta Choriodecidual Membrane-Derived Mesenchymal Stem Cells on Mitigating Endotoxin-Induced Mortality and Liver Injury in High-Fat Diet-Induced Obese Mice.

Publications

Let-7i-5p Mediates the Therapeutic Effects of Exosomes from Human Placenta Choriodecidual Membrane-Derived Mesenchymal Stem Cells on Mitigating Endotoxin-Induced Mortality and Liver Injury in High-Fat Diet-Induced Obese Mice.

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