Bovine milk exosomes contain microRNA and mRNA and are taken up by human macrophages.
We reported previously that microRNA (miRNA) are present in whey fractions of human breast milk, bovine milk, and rat milk. Moreover, we also confirmed that so many mRNA species are present in rat milk whey. These RNA were resistant to acidic conditions and to RNase, but were degraded by detergent. Thus, these RNA are likely packaged in membrane vesicles such as exosomes. However, functional extracellular circulating RNA in bodily fluids, such as blood miRNA, are present in various forms. In the current study, we used bovine raw milk and total RNA purified from exosomes (prepared by ultracentrifugation) and ultracentrifuged supernatants, and analyzed them using miRNA and mRNA microarrays to clarify which miRNA and mRNA species are present in exosomes, and which species exist in other forms. Microarray analyses revealed that most mRNA in milk whey were present in exosomes, whereas miRNA in milk whey were present in supernatant as well as exosomes. The RNA in exosomes might exert functional effects because of their stability. Therefore, we also investigated whether bovine milk-derived exosomes could affect human cells using THP-1 cells. Flow cytometry and fluorescent microscopy studies revealed that bovine milk exosomes were incorporated into differentiated THP-1 cells. These results suggest that bovine milk exosomes might have effects in human cells by containing RNA.
Nutritional Science Institute, Morinaga Milk Industry Co. Ltd., Zama, Kanagawa 252-8583, Japan. Electronic address: h-izumi@morinagamilk.co.jp.
Hirohisa
H
Izumi
Nutritional Science Institute, Morinaga Milk Industry Co. Ltd., Zama, Kanagawa 252-8583, Japan.
Muneya
M
Tsuda
Nutritional Science Institute, Morinaga Milk Industry Co. Ltd., Zama, Kanagawa 252-8583, Japan.
Yohei
Y
Sato
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Chuo-ku, Tokyo, 104-0045, Japan.
Nobuyoshi
N
Kosaka
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Chuo-ku, Tokyo, 104-0045, Japan.
Takahiro
T
Ochiya
Nutritional Science Institute, Morinaga Milk Industry Co. Ltd., Zama, Kanagawa 252-8583, Japan.
Hiroshi
H
Iwamoto
Nutritional Science Institute, Morinaga Milk Industry Co. Ltd., Zama, Kanagawa 252-8583, Japan.
Kazuyoshi
K
Namba
Nutritional Science Institute, Morinaga Milk Industry Co. Ltd., Zama, Kanagawa 252-8583, Japan.
Yasuhiro
Y
Takeda
D000818:Animals; D045744:Cell Line, Tumor; D055354:Exosomes / Q000737:chemistry*; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D008892:Milk / Q000737:chemistry*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism*; D000067796:Whey / Q000737:chemistry
D035683:MicroRNAs; D012333:RNA, Messenger
exosome; mRNA; microRNA; milk