Ding Zhenyu, Zhang Cuiyu, Zhang Baokun, Li Qin
Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Department of Physiology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, China.
Front Physiol. 2022 Feb 23;13:773671. doi: 10.3389/fphys.2022.773671. eCollection 2022.
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.
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.
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.
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.
本研究旨在鉴定小肠肠上皮细胞衍生外泌体(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。
分离雄性C57BL/6J小鼠的IECs。通过超速离心从空肠和回肠上皮细胞培养液中提取IEC-Exos。此外,采用相对和绝对定量同位素标记(iTRAQ)结合液相色谱-串联质谱(LC-MS/MS)检测IEC-Exo蛋白并进行生物信息分析。
结果显示,与空肠IEC-Exos相比,回肠IEC-Exos中有393种上调蛋白和346种下调蛋白。IECs-Exos,尤其是源自空肠的,富含血管紧张素转换酶2(ACE2)。回肠IEC-Exos中高表达的蛋白大多富集于遗传信息处理途径,主要介导胆汁酸转运、蛋白质合成及加工修饰过程。相比之下,空肠IEC-Exos中高表达的蛋白主要富集于涉及糖、脂肪酸、氨基酸、药物和骨代谢等的代谢途径。回肠和空肠IEC-Exos之间的差异表达蛋白不仅与消化系统功能有关,还与传染病、内分泌疾病和骨关节炎等的发生密切相关。
IEC-Exos在回肠和空肠之间存在许多差异表达蛋白,它们在调节肠道生物学功能中发挥不同作用。SARS-CoV-2的主要宿主细胞受体ACE2在IEC-Exos中高表达,这表明IEC-Exos可能是SARS-CoV-2感染的潜在途径。