The miR-7/EGFR axis controls the epithelial cell immunomodulation and regeneration and orchestrates the pathology in inflammatory bowel disease
Introduction: The epithelial immunomodulation and regeneration are intrinsic critical events against inflammatory bowel disease (IBD). MiR-7 is well documented as a promising regulator in the development of various diseases including inflammatory diseases. Objectives: This study aimed to assess the...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Journal of Advanced Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2090123223001170 |
| _version_ | 1797289724875898880 |
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| author | Juanjuan Zhao Mengmeng Guo Yaping Yan Ya Wang Xu Zhao Jing Yang Jing Chen Chao Chen Lin Tang Wenhuan Zeng Yiting Liu Ming Qin Ya Zhou Lin Xu |
| author_facet | Juanjuan Zhao Mengmeng Guo Yaping Yan Ya Wang Xu Zhao Jing Yang Jing Chen Chao Chen Lin Tang Wenhuan Zeng Yiting Liu Ming Qin Ya Zhou Lin Xu |
| author_sort | Juanjuan Zhao |
| collection | DOAJ |
| description | Introduction: The epithelial immunomodulation and regeneration are intrinsic critical events against inflammatory bowel disease (IBD). MiR-7 is well documented as a promising regulator in the development of various diseases including inflammatory diseases. Objectives: This study aimed to assess the effect of miR-7 in intestinal epithelial cells (IECs) in IBD. Methods: MiR-7def mice were given dextran sulfate sodium (DSS) to induce enteritis model. The infiltration of inflammatory cells was measured by FCM and immunofluorescence assay. 5′deletion assay and EMSA assays were performed to study the regulatory mechanism of miR-7 expression in IECs. The inflammatory signals and the targets of miR-7 were analyzed by RNA-seq and FISH assay. IECs were isolated from miR-7def, miR-7oe and WT mice to identify the immunomodulation and regeneration capacity. IEC-specific miR-7 silencing expression vector was designed and administered by the tail vein into murine DSS-induced enteritis model to evaluate the pathological lesions of IBD. Results: We found miR-7 deficiency improved the pathological lesions of DSS-induced murine enteritis model, accompanied by elevated proliferation and enhanced transduction of NF-κB/AKT/ERK signals in colonic IECs, as well as decreased local infiltration of inflammatory cells. MiR-7 was dominantly upregulated in colonic IECs in colitis. Moreover, the transcription of pre-miR-7a-1, orchestrated by transcription factor C/EBPα, was a main resource of mature miR-7 in IECs. As for the mechanism, EGFR, a miR-7 target gene, was downregulated in colonic IECs in colitis model and Crohn's disease patients. Furthermore, miR-7 also controlled the proliferation and inflammatory-cytokine secretion of IECs in response to inflammatory-signals through EGFR/NF-κB/AKT/ERK pathway. Finally, IEC-specific miR-7 silencing promoted the proliferation and transduction of NF-κB pathway in IECs and alleviated the pathological damage of colitis. Conclusion: Our results present the unknown role of miR-7/EGFR axis in IEC immunomodulation and regeneration in IBD and might provide clues for the application of miRNA-based therapeutic strategies in colonic diseases. |
| first_indexed | 2024-03-07T19:09:06Z |
| format | Article |
| id | doaj.art-352656930e774bea8008e26c627c15ad |
| institution | Directory Open Access Journal |
| issn | 2090-1232 |
| language | English |
| last_indexed | 2024-03-07T19:09:06Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
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| series | Journal of Advanced Research |
| spelling | doaj.art-352656930e774bea8008e26c627c15ad2024-03-01T05:05:52ZengElsevierJournal of Advanced Research2090-12322024-03-0157119134The miR-7/EGFR axis controls the epithelial cell immunomodulation and regeneration and orchestrates the pathology in inflammatory bowel diseaseJuanjuan Zhao0Mengmeng Guo1Yaping Yan2Ya Wang3Xu Zhao4Jing Yang5Jing Chen6Chao Chen7Lin Tang8Wenhuan Zeng9Yiting Liu10Ming Qin11Ya Zhou12Lin Xu13School of Medicine, Guizhou University, Guiyang 550025, Guizhou, China; Department of Immunology, Zunyi Medical University, Guizhou 563000, China; Key Laboratory of Gene Detection and Treatment of Guizhou Province, Guizhou, Zunyi 563000, ChinaDepartment of Immunology, Zunyi Medical University, Guizhou 563000, China; Key Laboratory of Gene Detection and Treatment of Guizhou Province, Guizhou, Zunyi 563000, ChinaDepartment of Immunology, Zunyi Medical University, Guizhou 563000, China; Key Laboratory of Gene Detection and Treatment of Guizhou Province, Guizhou, Zunyi 563000, ChinaDepartment of Immunology, Zunyi Medical University, Guizhou 563000, China; Key Laboratory of Gene Detection and Treatment of Guizhou Province, Guizhou, Zunyi 563000, ChinaDepartment of Immunology, Zunyi Medical University, Guizhou 563000, China; Key Laboratory of Gene Detection and Treatment of Guizhou Province, Guizhou, Zunyi 563000, ChinaDepartment of Immunology, Zunyi Medical University, Guizhou 563000, China; Key Laboratory of Gene Detection and Treatment of Guizhou Province, Guizhou, Zunyi 563000, ChinaDepartment of Immunology, Zunyi Medical University, Guizhou 563000, China; Key Laboratory of Gene Detection and Treatment of Guizhou Province, Guizhou, Zunyi 563000, ChinaDepartment of Immunology, Zunyi Medical University, Guizhou 563000, China; Key Laboratory of Gene Detection and Treatment of Guizhou Province, Guizhou, Zunyi 563000, ChinaDepartment of Immunology, Zunyi Medical University, Guizhou 563000, China; Key Laboratory of Gene Detection and Treatment of Guizhou Province, Guizhou, Zunyi 563000, ChinaKey Laboratory of Gene Detection and Treatment of Guizhou Province, Guizhou, Zunyi 563000, ChinaKey Laboratory of Gene Detection and Treatment of Guizhou Province, Guizhou, Zunyi 563000, ChinaDepartment of Immunology, Zunyi Medical University, Guizhou 563000, China; Key Laboratory of Gene Detection and Treatment of Guizhou Province, Guizhou, Zunyi 563000, ChinaDepartment of Medical Physics, Zunyi Medical University, Guizhou 563000, China; Key Laboratory of Gene Detection and Treatment of Guizhou Province, Guizhou, Zunyi 563000, ChinaSchool of Medicine, Guizhou University, Guiyang 550025, Guizhou, China; Department of Immunology, Zunyi Medical University, Guizhou 563000, China; Key Laboratory of Gene Detection and Treatment of Guizhou Province, Guizhou, Zunyi 563000, China; Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, Guizhou 563000, China; Corresponding author at: Department of Immunology, Zunyi Medical University, Guizhou Province 563000, China.Introduction: The epithelial immunomodulation and regeneration are intrinsic critical events against inflammatory bowel disease (IBD). MiR-7 is well documented as a promising regulator in the development of various diseases including inflammatory diseases. Objectives: This study aimed to assess the effect of miR-7 in intestinal epithelial cells (IECs) in IBD. Methods: MiR-7def mice were given dextran sulfate sodium (DSS) to induce enteritis model. The infiltration of inflammatory cells was measured by FCM and immunofluorescence assay. 5′deletion assay and EMSA assays were performed to study the regulatory mechanism of miR-7 expression in IECs. The inflammatory signals and the targets of miR-7 were analyzed by RNA-seq and FISH assay. IECs were isolated from miR-7def, miR-7oe and WT mice to identify the immunomodulation and regeneration capacity. IEC-specific miR-7 silencing expression vector was designed and administered by the tail vein into murine DSS-induced enteritis model to evaluate the pathological lesions of IBD. Results: We found miR-7 deficiency improved the pathological lesions of DSS-induced murine enteritis model, accompanied by elevated proliferation and enhanced transduction of NF-κB/AKT/ERK signals in colonic IECs, as well as decreased local infiltration of inflammatory cells. MiR-7 was dominantly upregulated in colonic IECs in colitis. Moreover, the transcription of pre-miR-7a-1, orchestrated by transcription factor C/EBPα, was a main resource of mature miR-7 in IECs. As for the mechanism, EGFR, a miR-7 target gene, was downregulated in colonic IECs in colitis model and Crohn's disease patients. Furthermore, miR-7 also controlled the proliferation and inflammatory-cytokine secretion of IECs in response to inflammatory-signals through EGFR/NF-κB/AKT/ERK pathway. Finally, IEC-specific miR-7 silencing promoted the proliferation and transduction of NF-κB pathway in IECs and alleviated the pathological damage of colitis. Conclusion: Our results present the unknown role of miR-7/EGFR axis in IEC immunomodulation and regeneration in IBD and might provide clues for the application of miRNA-based therapeutic strategies in colonic diseases.http://www.sciencedirect.com/science/article/pii/S2090123223001170Inflammatory bowel diseaseMiR-7Immune cellsIntestinal epithelial cellsEGFR |
| spellingShingle | Juanjuan Zhao Mengmeng Guo Yaping Yan Ya Wang Xu Zhao Jing Yang Jing Chen Chao Chen Lin Tang Wenhuan Zeng Yiting Liu Ming Qin Ya Zhou Lin Xu The miR-7/EGFR axis controls the epithelial cell immunomodulation and regeneration and orchestrates the pathology in inflammatory bowel disease Journal of Advanced Research Inflammatory bowel disease MiR-7 Immune cells Intestinal epithelial cells EGFR |
| title | The miR-7/EGFR axis controls the epithelial cell immunomodulation and regeneration and orchestrates the pathology in inflammatory bowel disease |
| title_full | The miR-7/EGFR axis controls the epithelial cell immunomodulation and regeneration and orchestrates the pathology in inflammatory bowel disease |
| title_fullStr | The miR-7/EGFR axis controls the epithelial cell immunomodulation and regeneration and orchestrates the pathology in inflammatory bowel disease |
| title_full_unstemmed | The miR-7/EGFR axis controls the epithelial cell immunomodulation and regeneration and orchestrates the pathology in inflammatory bowel disease |
| title_short | The miR-7/EGFR axis controls the epithelial cell immunomodulation and regeneration and orchestrates the pathology in inflammatory bowel disease |
| title_sort | mir 7 egfr axis controls the epithelial cell immunomodulation and regeneration and orchestrates the pathology in inflammatory bowel disease |
| topic | Inflammatory bowel disease MiR-7 Immune cells Intestinal epithelial cells EGFR |
| url | http://www.sciencedirect.com/science/article/pii/S2090123223001170 |
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