College of Animal Science, South China Agricultural University, 483 Wushan Road, Tianhe District, Guangzhou, Guangdong 510642, China; Collaborative Innovation Center of Plant Pest Management and Bioenvironmental Health Application Technology, Guangdong Eco-Engineering Polytechnic, 297 Guangshan First Road, Tianhe District, Guangzhou, Guangdong 510520, China; Guangdong Province Key Laboratory of Animal Nutritional Regulation, 483 Wushan Road, Tianhe District, Guangzhou, Guangdong 510642, China.
College of Animal Science, South China Agricultural University, 483 Wushan Road, Tianhe District, Guangzhou, Guangdong 510642, China; Guangdong Province Key Laboratory of Animal Nutritional Regulation, 483 Wushan Road, Tianhe District, Guangzhou, Guangdong 510642, China; National Engineering Research Center for Breeding Swine Industry, 483 Wushan Road, Tianhe District, Guangzhou, Guangdong 510642, China; Guangdong Engineering＆Research Center for Woody Fodder Plants, 483 Wushan Road, Tianhe District, Guangzhou, Guangdong 510642, China.
Biochem Pharmacol. 2020 May;175:113898. doi: 10.1016/j.bcp.2020.113898. Epub 2020 Mar 4.
Porcine milk exosomes play an important role in mother-infant communication. Deoxynivalenol (DON) is a toxin which causes serious damage to the animal intestinal mucosa. Our previous study showed porcine milk exosomes facilitate mice intestine development, but the effects of these exosomes to antagonize DON toxicity is unclear. Our in vivo results showed that milk exosomes attenuated DON-induced damage on the mouse body weight and intestinal epithelium growth. In addition, these exosomes could reverse DON-induced inhibition on cell proliferation and tight junction proteins (TJs) formation and reduce DON-induced cell apoptosis. In vitro, exosomes up-regulated the expression of miR-181a, miR-30c, miR-365-5p and miR-769-3p in IPEC-J2 cells and then down-regulated the expression of their targeting genes in p53 pathway, ultimately attenuating DON-induced damage by promoting cell proliferation and TJs and by inhibiting cell apoptosis. In conclusion, porcine milk exosomes could protect the intestine against DON damage, and these protections may take place through the miRNAs in exosomes. These results indicated that the addition of miRNA-enriched exosomes to feed or food could be used as a novel preventative measure for necrotizing enterocolitis.
猪乳外泌体在母婴沟通中发挥重要作用。脱氧雪腐镰刀菌烯醇（DON）是一种毒素，会对动物的肠道黏膜造成严重损害。我们之前的研究表明，猪乳外泌体促进了小鼠肠道的发育，但这些外泌体拮抗 DON 毒性的作用尚不清楚。我们的体内研究结果表明，乳外泌体减轻了 DON 诱导的小鼠体重和肠道上皮生长损伤。此外，这些外泌体还可以逆转 DON 对细胞增殖和紧密连接蛋白（TJs）形成的抑制作用，并减少 DON 诱导的细胞凋亡。体外实验中，外泌体上调了 IPEC-J2 细胞中 miR-181a、miR-30c、miR-365-5p 和 miR-769-3p 的表达，进而下调了 p53 通路中这些靶向基因的表达，最终通过促进细胞增殖和 TJs 形成并抑制细胞凋亡，减轻 DON 诱导的损伤。综上所述，猪乳外泌体可以保护肠道免受 DON 损伤，而这些保护作用可能是通过外泌体中的 miRNAs 实现的。这些结果表明，在饲料或食物中添加富含 miRNA 的外泌体可能成为一种防治坏死性小肠结肠炎的新预防措施。
