Serum Exosomes Derived from Irritable Bowel Syndrome Patient Increase Cell Permeability via Regulating miR-148b-5p/RGS2 Signaling in Human Colonic Epithelium Cells

Aim. Irritable bowel syndrome (IBS) is a multifactorial functional bowel disorder characterized by disruption of the intestinal barrier. Circulating exosomal microRNAs (miRNAs) are involved in regulating epithelial barrier function, and upregulation of miR-148b-5p has been detected in IBS. However,...

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Main Authors: Ying Xing, Shan Xue, Jing Wu, Jianhong Zhou, Fangfang Xing, Tianxing Li, Xiaohu Nie
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:Gastroenterology Research and Practice
Online Access:http://dx.doi.org/10.1155/2021/6655900
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author Ying Xing
Shan Xue
Jing Wu
Jianhong Zhou
Fangfang Xing
Tianxing Li
Xiaohu Nie
author_facet Ying Xing
Shan Xue
Jing Wu
Jianhong Zhou
Fangfang Xing
Tianxing Li
Xiaohu Nie
author_sort Ying Xing
collection DOAJ
description Aim. Irritable bowel syndrome (IBS) is a multifactorial functional bowel disorder characterized by disruption of the intestinal barrier. Circulating exosomal microRNAs (miRNAs) are involved in regulating epithelial barrier function, and upregulation of miR-148b-5p has been detected in IBS. However, whether exosomal miR-148-5p is involved in the IBS pathogenesis remains unclear. This study was aimed at investigating the relationship of exosomal miR-148-5p with colonic epithelial permeability. Methods. Exosomes were isolated from the serum of IBS patients and healthy controls. HT-29 cells were cultured with the IBS-derived serum exosomes (IBS-exo). Exosome uptake assay was used to evaluate whether the IBS-exo could be absorbed by HT-29 cells. FITC-Dextran flux and transepithelial/endothelial electrical resistance were measured to evaluate epithelial permeability. A luciferase reporter assay was used to determine whether the regulator of G protein signaling- (RGS-) 2 is a target gene of miR-148b-5p. Results. miR-148b-5p was obviously elevated in the IBS-exo compared to the control-exo. Upregulation of miR-148b-5p was observed in the HT-29 cells cultured with IBS-exo. Exposure to IBS-exo increased cell permeability and decreased RGS2 expression. The IBS-exo-induced alterations were obviously reversed by interfering with the miR-148b-5p expression. Mimicking the IBS-exo treatment, miR-148b-5p overexpression increased cell permeability and downregulated RGS2 expression, which were abrogated by overexpressing RGS2. The luciferase reporter assay revealed that RGS2 was a direct target of miR-148b-5p. Conclusions. Serum-derived exosomes from IBS patients increase colonic epithelial permeability via miR-148b-5p/RGS2 signaling.
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spelling doaj-art-cbeee083c67743a28c233b60418fae162025-08-20T03:23:35ZengWileyGastroenterology Research and Practice1687-61211687-630X2021-01-01202110.1155/2021/66559006655900Serum Exosomes Derived from Irritable Bowel Syndrome Patient Increase Cell Permeability via Regulating miR-148b-5p/RGS2 Signaling in Human Colonic Epithelium CellsYing Xing0Shan Xue1Jing Wu2Jianhong Zhou3Fangfang Xing4Tianxing Li5Xiaohu Nie6Department of Gastroenterology, 72nd Group Army Hospital, Huzhou University, Huzhou 313000, Zhejiang, ChinaDepartment of Gastroenterology, 72nd Group Army Hospital, Huzhou University, Huzhou 313000, Zhejiang, ChinaDepartment of Gastroenterology, 72nd Group Army Hospital, Huzhou University, Huzhou 313000, Zhejiang, ChinaDepartment of Gastroenterology, 72nd Group Army Hospital, Huzhou University, Huzhou 313000, Zhejiang, ChinaDepartment of Gastroenterology, 72nd Group Army Hospital, Huzhou University, Huzhou 313000, Zhejiang, ChinaDepartment of Gastroenterology, 72nd Group Army Hospital, Huzhou University, Huzhou 313000, Zhejiang, ChinaHuzhou Central Hospital, Affiliated Central Hospital of Huzhou University, Huzhou 313000, Zhejiang, ChinaAim. Irritable bowel syndrome (IBS) is a multifactorial functional bowel disorder characterized by disruption of the intestinal barrier. Circulating exosomal microRNAs (miRNAs) are involved in regulating epithelial barrier function, and upregulation of miR-148b-5p has been detected in IBS. However, whether exosomal miR-148-5p is involved in the IBS pathogenesis remains unclear. This study was aimed at investigating the relationship of exosomal miR-148-5p with colonic epithelial permeability. Methods. Exosomes were isolated from the serum of IBS patients and healthy controls. HT-29 cells were cultured with the IBS-derived serum exosomes (IBS-exo). Exosome uptake assay was used to evaluate whether the IBS-exo could be absorbed by HT-29 cells. FITC-Dextran flux and transepithelial/endothelial electrical resistance were measured to evaluate epithelial permeability. A luciferase reporter assay was used to determine whether the regulator of G protein signaling- (RGS-) 2 is a target gene of miR-148b-5p. Results. miR-148b-5p was obviously elevated in the IBS-exo compared to the control-exo. Upregulation of miR-148b-5p was observed in the HT-29 cells cultured with IBS-exo. Exposure to IBS-exo increased cell permeability and decreased RGS2 expression. The IBS-exo-induced alterations were obviously reversed by interfering with the miR-148b-5p expression. Mimicking the IBS-exo treatment, miR-148b-5p overexpression increased cell permeability and downregulated RGS2 expression, which were abrogated by overexpressing RGS2. The luciferase reporter assay revealed that RGS2 was a direct target of miR-148b-5p. Conclusions. Serum-derived exosomes from IBS patients increase colonic epithelial permeability via miR-148b-5p/RGS2 signaling.http://dx.doi.org/10.1155/2021/6655900
spellingShingle Ying Xing
Shan Xue
Jing Wu
Jianhong Zhou
Fangfang Xing
Tianxing Li
Xiaohu Nie
Serum Exosomes Derived from Irritable Bowel Syndrome Patient Increase Cell Permeability via Regulating miR-148b-5p/RGS2 Signaling in Human Colonic Epithelium Cells
Gastroenterology Research and Practice
title Serum Exosomes Derived from Irritable Bowel Syndrome Patient Increase Cell Permeability via Regulating miR-148b-5p/RGS2 Signaling in Human Colonic Epithelium Cells
title_full Serum Exosomes Derived from Irritable Bowel Syndrome Patient Increase Cell Permeability via Regulating miR-148b-5p/RGS2 Signaling in Human Colonic Epithelium Cells
title_fullStr Serum Exosomes Derived from Irritable Bowel Syndrome Patient Increase Cell Permeability via Regulating miR-148b-5p/RGS2 Signaling in Human Colonic Epithelium Cells
title_full_unstemmed Serum Exosomes Derived from Irritable Bowel Syndrome Patient Increase Cell Permeability via Regulating miR-148b-5p/RGS2 Signaling in Human Colonic Epithelium Cells
title_short Serum Exosomes Derived from Irritable Bowel Syndrome Patient Increase Cell Permeability via Regulating miR-148b-5p/RGS2 Signaling in Human Colonic Epithelium Cells
title_sort serum exosomes derived from irritable bowel syndrome patient increase cell permeability via regulating mir 148b 5p rgs2 signaling in human colonic epithelium cells
url http://dx.doi.org/10.1155/2021/6655900
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