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

Chao Yuan Chang, Kung Yen Chen, Hung Jen Shih, Milton Chiang, I. Tao Huang, Yen Hua Huang, Chun Jen Huang

研究成果: 雜誌貢獻文章同行評審

1 引文 斯高帕斯(Scopus)

摘要

Obesity complicates sepsis and increases the mortality of sepsis. We examined the effects of exosomes (from human placenta choriodecidual membrane-derived mesenchymal stem cells, pcM-SCs) 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 sur-viving mice, by contrast, levels of liver injury (injury score, plasma aspartate transaminase and alanine transaminase concentrations, tissue water content, and leukocyte infiltration in liver tis-sues; 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 in-jury/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.
原文英語
文章編號36
期刊Pharmaceuticals
15
發行號1
DOIs
出版狀態已發佈 - 1月 2022

ASJC Scopus subject areas

  • 分子醫學
  • 藥學科學
  • 藥物發現

指紋

深入研究「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」主題。共同形成了獨特的指紋。

引用此