Adipocyte metabolism is improved by TNF receptor-targeting small RNAs identified from dried nuts

被引:76
作者
Aquilano, Katia [1 ]
Ceci, Veronica [1 ]
Gismondi, Angelo [1 ]
De Stefano, Susanna [2 ]
Iacovelli, Federico [1 ]
Faraonio, Raffaella [3 ]
Di Marcos, Gabriele [1 ]
Poerio, Noemi [1 ]
Minutolo, Antonella [1 ]
Minopoli, Giuseppina [3 ]
Marcone, Antonia [3 ]
Fraziano, Maurizio [1 ]
Tortolici, Flavia [1 ]
Sennato, Simona [4 ,5 ]
Casciardi, Stefano [6 ]
Potesta, Marina [1 ]
Bernardini, Roberta [7 ]
Mattei, Maurizio [1 ,7 ]
Falconi, Mattia [1 ]
Montesano, Carla [1 ]
Rufini, Stefano [1 ]
Canini, Antonella [1 ]
Lettieri-Barbato, Daniele [1 ,8 ]
机构
[1] Univ Roma Tor Vergata, Dept Biol, Rome, Italy
[2] Univ Roma Tor Vergata, Dept Chem Sci & Technol, Rome, Italy
[3] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, Naples, Italy
[4] Sapienza Univ Rome, CNR ISC, Piazzale A Moro 2, I-00185 Rome, Italy
[5] Sapienza Univ Rome, Dept Phys, Piazzale A Moro 2, I-00185 Rome, Italy
[6] Natl Inst Insurance Accid Work INAIL Res, Dept Occupat & Environm Med Epidemiol & Hyg, Rome, Italy
[7] Univ Roma Tor Vergata, Interdept Serv Ctr, Stn Anima Technol STA, Rome, Italy
[8] IRCCS Fdn Santa Lucia, I-00143 Rome, Italy
基金
欧盟地平线“2020”;
关键词
NECROSIS-FACTOR-ALPHA; ADIPOSE-TISSUE; INSULIN-RESISTANCE; MOLECULAR INSIGHTS; GENE-EXPRESSION; OBESITY; PREDICTION; ACCURATE; MIRNAS;
D O I
10.1038/s42003-019-0563-7
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
There is a growing interest in therapeutically targeting the inflammatory response that underlies age-related chronic diseases including obesity and type 2 diabetes. Through integrative small RNA sequencing, we show the presence of conserved plant miR159a and miR156c in dried nuts having high complementarity with the mammalian TNF receptor superfamily member 1a (Tnfrsf1a) transcript. We detected both miR159a and miR156c in exosome-like nut nanovesicles (NVs) and demonstrated that such NVs reduce Tnfrsf1a protein and dampen TNF-alpha signaling pathway in adipocytes. Synthetic single-stranded microRNAs (ss-miRs) modified with 2'-O-methyl group function as miR mimics. In plants, this modification naturally occurs on nearly all small RNAs. 2'-O-methylated ss-miR mimics for miR156c and miR159a decreased Tnfrsf1a protein and inflammatory markers in hypertrophic as well as TNF-alpha-treated adipocytes and macrophages. miR156c and miR159a mimics effectively suppress inflammation in mice, highlighting a potential role of plant miR-based, single-stranded oligonucleotides in treating inflammatory-associated metabolic diseases.
引用
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页数:13
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