Unraveling the Proteomic Landscape of Intestinal Epithelial Cell-Derived Exosomes in Mice.

Unraveling the Proteomic Landscape of Intestinal Epithelial Cell-Derived Exosomes in Mice.
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揭示小鼠肠上皮细胞来源的外泌体的蛋白质组学景观

DOI:
10.3389/fphys.2022.773671
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发表时间:
2022
影响因子:
4
通讯作者:
Li Q
Li Q
中科院分区:
医学2区
文献类型:
--
作者:
Ding Z;Zhang C;Zhang B;Li Q

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目的研究小肠肠上皮细胞源性exosomes(IEC-Exos)的生物学功能,并进一步区分回肠和空肠IEC-Exos中与消化系统功能及多种疾病发生相关的差异蛋白。材料与方法分离雄性C57 BL/6 J小鼠IEC。采用超离心法从空肠和回肠上皮细胞培养液中提取IEC-Exos。此外,同量异位素相对和绝对定量标签(iTRAQ)结合液相色谱-串联质谱(LC-MS/MS)用于检测IEC-Exo蛋白并进行生物信息分析。结果与空肠IEC-Exos相比,回肠IEC-Exos表达上调的蛋白有393个,下调的蛋白有346个。肠源性肠上皮细胞富含血管紧张素转换酶2(ACE 2)。回肠IEC-Exos高表达蛋白主要富集在遗传信息处理途径,主要介导胆汁酸转运、蛋白质合成和加工修饰等过程。空肠IEC-Exos高表达蛋白主要富集在糖、脂肪酸、氨基酸、药物、骨代谢等代谢途径中,回肠和空肠IEC-Exos差异表达蛋白不仅与消化系统功能有关,而且与感染性疾病、内分泌疾病、骨关节炎的发生密切相关,结论IEC-Exos中回肠和空肠之间存在许多差异表达的蛋白质,它们在调节肠道生物学功能方面发挥着不同的作用。SARS-CoV-2的主要宿主细胞受体ACE 2在IEC-Exos中高表达,提示IEC-Exos可能是SARS-CoV-2感染的一条潜在途径。
Purpose This study aimed to identify the biological functions of small intestine intestinal epithelial cell derived exosomes (IEC-Exos) and further distinguished the difference proteins in IEC-Exos between ileum and jejunum related to function of the digestive system and occurrence of several diseases. Materials and Methods IECs of Male C57BL/6J mice were isolated. IEC-Exos were extracted from jejunum and ileum epithelial cell culture fluid by ultracentrifugation. In addition, isobaric tags for relative and absolute quantitation (iTRAQ) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to detect IEC-Exo proteins and conduct biological information analysis. Results The results showed that compared with jejunum IEC-Exos from ileum IEC-Exos, there were 393 up-regulated proteins and 346 down-regulated proteins. IECs-Exos, especially derived from jejunum, were rich in angiotensin-converting enzyme 2 (ACE2). The highly expressed proteins from ileum IEC-Exos were mostly enriched in genetic information processing pathways, which mainly mediate the processes of bile acid transport, protein synthesis and processing modification. In contrast, the highly expressed proteins from jejunum IEC-Exos were mainly enriched in metabolic pathways involved in sugar, fatty acid, amino acid, drug, and bone metabolism, etc. The differentially expressed proteins between ileum and jejunum IEC-Exos were not only related to the function of the digestive system but also closely related to the occurrence of infectious diseases, endocrine diseases and osteoarthritis, etc. Conclusion IEC-Exos there were many differentially expressed proteins between ileum and jejunum, which played different roles in regulating intestinal biological functions. ACE2, the main host cell receptor of SARS-CoV-2, was highly expressed in IEC-Exos, which indicated that IEC-Exos may be a potential route of SARS-CoV-2 infection.
DOI: 10.1126/science.aau6977
发表时间: 2020-02-07
期刊: Science (New York, N.Y.)
影响因子: --
作者:
Kalluri R;LeBleu VS
通讯作者: LeBleu VS
DOI: 10.1080/10409238.2020.1768207
发表时间: 2020-04
影响因子: 6.5
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通讯作者: Golczak M
DOI: 10.1016/j.biochi.2007.03.009
发表时间: 2007-08-01
期刊: BIOCHIMIE
影响因子: 3.9
作者:
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DOI: 10.1126/science.abc1669
发表时间: 2020-07-03
期刊: SCIENCE
影响因子: 56.9
作者:
Lamers, Mart M.;Beumer, Joep;Clevers, Hans
通讯作者: Clevers, Hans
DOI: 10.1152/physiolgenomics.00139.2017
发表时间: 2018-06-01
影响因子: 4.6
作者:
O'Brien, Patrick;Hewett, Rhys;Corpe, Christopher
通讯作者: Corpe, Christopher