Abstract

PurposeThis 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 MethodsIECs 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.ResultsThe 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.ConclusionIEC-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.

Highlights

  • Intestinal epithelial cells (IECs), which have the characteristics of continuous migration, differentiation, and renewal, play an important role in maintaining intestinal function

  • The results of nanoparticle tracking analysis showed that the concentration of ileum IEC-Exos was 1.0E + 8 particles/mL, and the diameter of IEC-Exos was mainly concentrated at 30–130 nm

  • Based on previously reported cell type–specific markers and intestinal single-cell sequencing results(Haber et al, 2017; Wang Y. et al, 2020), we confirmed that the IEC-Exos we isolated were mainly derived from eight known intestinal epithelial cells, including enterocyte cells, goblet cells, Paneth cells, enteroendocrine cells, tuft cells, progenitor cells, transit amplifying cells (TACs) and stem cells (Schedule 2)

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Summary

Introduction

Intestinal epithelial cells (IECs), which have the characteristics of continuous migration, differentiation, and renewal, play an important role in maintaining intestinal function. The intestine is involved in drug metabolism, energy metabolism, Unraveling Intestinal Epithelial Cell-Derived Exosomes endocrine responses, oxidative stress, and immune defense mechanisms (Peterson and Artis, 2014; Kiela and Ghishan, 2016; Satsu, 2017). Angiotensin-converting enzyme 2 (ACE2), which is highly expressed on IECs, is a receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected cells and has an important effect on the occurrence and development of coronavirus disease 2019 (COVID-19) (Lamers et al, 2020; Ziegler et al, 2020). Intestinal epithelial cell derived exosomes (IEC-Exos) have not been studied in detail. Many significant biological functions, and mechanisms of IEC-Exos have not been fully elucidated

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