Moxibustion Regulates the BRG1/Nrf2/HO-1 Pathway by Inhibiting MicroRNA-222-3p to Prevent Oxidative Stress in Intestinal Epithelial Cells in Ulcerative Colitis and Colitis-Associated Colorectal Cancer

Oxidative stress is crucial in ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC). Intestinal epithelial cells (IECs) are an important component of the intestinal barrier. In previous studies, we have demonstrated that suppressing microRNA-222-3p (miR-222-3p) can protect against...

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Main Authors: Xuejun Wang, Haiyang Ji, Yanting Yang, Dan Zhang, Xiehe Kong, Xiaoying Li, Hongna Li, Yunqiong Lu, Guang Yang, Jie Liu, Huangan Wu, Jue Hong, Xiaopeng Ma
Format: Article
Language:English
Published: Wiley 2024-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2024/8273732
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author Xuejun Wang
Haiyang Ji
Yanting Yang
Dan Zhang
Xiehe Kong
Xiaoying Li
Hongna Li
Yunqiong Lu
Guang Yang
Jie Liu
Huangan Wu
Jue Hong
Xiaopeng Ma
author_facet Xuejun Wang
Haiyang Ji
Yanting Yang
Dan Zhang
Xiehe Kong
Xiaoying Li
Hongna Li
Yunqiong Lu
Guang Yang
Jie Liu
Huangan Wu
Jue Hong
Xiaopeng Ma
author_sort Xuejun Wang
collection DOAJ
description Oxidative stress is crucial in ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC). Intestinal epithelial cells (IECs) are an important component of the intestinal barrier. In previous studies, we have demonstrated that suppressing microRNA-222-3p (miR-222-3p) can protect against oxidative stress in IECs, which ameliorates colonic injuries in UC mice and prevents the conversion of UC to CAC. In this case, we hope to explore whether moxibustion can alleviate UC and CAC by inhibiting miR-222-3p based on mouse models of UC and CAC. After herb-partitioned moxibustion (HPM) intervention, the disease activity index (DAI) and colon macroscopic damage index (CMDI) were significantly reduced in UC mice, and the number and volume of intestinal tumors were decreased considerably in CAC mice. Meanwhile, we found that HPM suppressed miR-222-3p expression and upregulated the mRNA and protein expression of Brahma-related gene 1 (BRG1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), while inhibiting Kelch-like ECH-associated protein 1 (Keap1) expression in IECs of UC and CAC mice. With changes in reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α), we verified that HPM protects against oxidative stress and inflammation in IECs of UC and CAC mice. The effect of HPM was inhibited in miR-222-3p overexpression mice, further demonstrating that the protective effect of HPM on UC and CAC mice was through inhibiting miR-222-3p. In summary, HPM regulates the BRG1/Nrf2/HO-1 pathway by inhibiting miR-222-3p to attenuate oxidative stress in IECs in UC and CAC.
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spelling doaj-art-62a363e5734145adb1ea2201d36bfb672025-02-03T11:54:52ZengWileyJournal of Immunology Research2314-71562024-01-01202410.1155/2024/8273732Moxibustion Regulates the BRG1/Nrf2/HO-1 Pathway by Inhibiting MicroRNA-222-3p to Prevent Oxidative Stress in Intestinal Epithelial Cells in Ulcerative Colitis and Colitis-Associated Colorectal CancerXuejun Wang0Haiyang Ji1Yanting Yang2Dan Zhang3Xiehe Kong4Xiaoying Li5Hongna Li6Yunqiong Lu7Guang Yang8Jie Liu9Huangan Wu10Jue Hong11Xiaopeng Ma12Yueyang Hospital of Integrated Traditional Chinese and Western MedicineYueyang Hospital of Integrated Traditional Chinese and Western MedicineYueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai Research Institute of Acupuncture and MeridianYueyang Hospital of Integrated Traditional Chinese and Western MedicineYueyang Hospital of Integrated Traditional Chinese and Western MedicineYueyang Hospital of Integrated Traditional Chinese and Western MedicineYueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai Research Institute of Acupuncture and MeridianShanghai Research Institute of Acupuncture and MeridianYueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai Research Institute of Acupuncture and MeridianYueyang Hospital of Integrated Traditional Chinese and Western MedicineOxidative stress is crucial in ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC). Intestinal epithelial cells (IECs) are an important component of the intestinal barrier. In previous studies, we have demonstrated that suppressing microRNA-222-3p (miR-222-3p) can protect against oxidative stress in IECs, which ameliorates colonic injuries in UC mice and prevents the conversion of UC to CAC. In this case, we hope to explore whether moxibustion can alleviate UC and CAC by inhibiting miR-222-3p based on mouse models of UC and CAC. After herb-partitioned moxibustion (HPM) intervention, the disease activity index (DAI) and colon macroscopic damage index (CMDI) were significantly reduced in UC mice, and the number and volume of intestinal tumors were decreased considerably in CAC mice. Meanwhile, we found that HPM suppressed miR-222-3p expression and upregulated the mRNA and protein expression of Brahma-related gene 1 (BRG1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), while inhibiting Kelch-like ECH-associated protein 1 (Keap1) expression in IECs of UC and CAC mice. With changes in reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α), we verified that HPM protects against oxidative stress and inflammation in IECs of UC and CAC mice. The effect of HPM was inhibited in miR-222-3p overexpression mice, further demonstrating that the protective effect of HPM on UC and CAC mice was through inhibiting miR-222-3p. In summary, HPM regulates the BRG1/Nrf2/HO-1 pathway by inhibiting miR-222-3p to attenuate oxidative stress in IECs in UC and CAC.http://dx.doi.org/10.1155/2024/8273732
spellingShingle Xuejun Wang
Haiyang Ji
Yanting Yang
Dan Zhang
Xiehe Kong
Xiaoying Li
Hongna Li
Yunqiong Lu
Guang Yang
Jie Liu
Huangan Wu
Jue Hong
Xiaopeng Ma
Moxibustion Regulates the BRG1/Nrf2/HO-1 Pathway by Inhibiting MicroRNA-222-3p to Prevent Oxidative Stress in Intestinal Epithelial Cells in Ulcerative Colitis and Colitis-Associated Colorectal Cancer
Journal of Immunology Research
title Moxibustion Regulates the BRG1/Nrf2/HO-1 Pathway by Inhibiting MicroRNA-222-3p to Prevent Oxidative Stress in Intestinal Epithelial Cells in Ulcerative Colitis and Colitis-Associated Colorectal Cancer
title_full Moxibustion Regulates the BRG1/Nrf2/HO-1 Pathway by Inhibiting MicroRNA-222-3p to Prevent Oxidative Stress in Intestinal Epithelial Cells in Ulcerative Colitis and Colitis-Associated Colorectal Cancer
title_fullStr Moxibustion Regulates the BRG1/Nrf2/HO-1 Pathway by Inhibiting MicroRNA-222-3p to Prevent Oxidative Stress in Intestinal Epithelial Cells in Ulcerative Colitis and Colitis-Associated Colorectal Cancer
title_full_unstemmed Moxibustion Regulates the BRG1/Nrf2/HO-1 Pathway by Inhibiting MicroRNA-222-3p to Prevent Oxidative Stress in Intestinal Epithelial Cells in Ulcerative Colitis and Colitis-Associated Colorectal Cancer
title_short Moxibustion Regulates the BRG1/Nrf2/HO-1 Pathway by Inhibiting MicroRNA-222-3p to Prevent Oxidative Stress in Intestinal Epithelial Cells in Ulcerative Colitis and Colitis-Associated Colorectal Cancer
title_sort moxibustion regulates the brg1 nrf2 ho 1 pathway by inhibiting microrna 222 3p to prevent oxidative stress in intestinal epithelial cells in ulcerative colitis and colitis associated colorectal cancer
url http://dx.doi.org/10.1155/2024/8273732
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