Role of the nuclear receptor subfamily 4a in mast cells in the development of irritable bowel syndrome
The activation of mast cells (MCs) and mediator release are closely related to the pathophysiology of irritable bowel syndrome (IBS). However, the exact underlying mechanisms are still not completely understood. The nuclear receptor subfamily 4a (Nr4a) is a family of orphan nuclear receptors implica...
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Elsevier
2022-01-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037022000575 |
| _version_ | 1828088050891096064 |
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| author | Ruidi Li Shuhui Chen Xinpei Gu Shuhong An Zhaojin Wang |
| author_facet | Ruidi Li Shuhui Chen Xinpei Gu Shuhong An Zhaojin Wang |
| author_sort | Ruidi Li |
| collection | DOAJ |
| description | The activation of mast cells (MCs) and mediator release are closely related to the pathophysiology of irritable bowel syndrome (IBS). However, the exact underlying mechanisms are still not completely understood. The nuclear receptor subfamily 4a (Nr4a) is a family of orphan nuclear receptors implicated in regulating MC activation, degranulation, cytokine/chemokine synthesis and release. Acute and chronic stress trigger hypothalamic–pituitaryadrenal axis (HPA) activation to induce the release of corticotropin-releasing hormone (CRH), resulting in MC activation and induction of the Nr4a family. Our newest data showed that Nr4a members were specially over-expressed in colonic MCs of the chronic water-avoidance stress (WAS)-induced visceral hyperalgesia mice, suggesting that Nr4a members might be involved in the pathophysiology of visceral hypersensitivity. In this review, we highlight the present knowledge on roles of Nr4a members in the activation of MCs and the pathophysiology of IBS, and discuss signaling pathways that modulate the activation of Nr4a family members. We propose that a better understanding of Nr4a members and their modulators may facilitate the development of more selective and effective therapies to treat IBS patients. |
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| format | Article |
| id | doaj.art-73e5d231ba354a01adfb620c1ebdabf5 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-04-11T05:20:26Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
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| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-73e5d231ba354a01adfb620c1ebdabf52022-12-24T04:51:32ZengElsevierComputational and Structural Biotechnology Journal2001-03702022-01-012011981207Role of the nuclear receptor subfamily 4a in mast cells in the development of irritable bowel syndromeRuidi Li0Shuhui Chen1Xinpei Gu2Shuhong An3Zhaojin Wang4Department of Human Anatomy, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, ChinaDepartment of Human Anatomy, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, ChinaDepartment of Human Anatomy, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, ChinaCorresponding authors at: Department of Human Anatomy, Shandong First Medical University & Shandong Academy of Medical Sciences, 2 Ying Sheng Dong Lu, Taian 271000, China.; Department of Human Anatomy, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, ChinaCorresponding authors at: Department of Human Anatomy, Shandong First Medical University & Shandong Academy of Medical Sciences, 2 Ying Sheng Dong Lu, Taian 271000, China.; Department of Human Anatomy, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, ChinaThe activation of mast cells (MCs) and mediator release are closely related to the pathophysiology of irritable bowel syndrome (IBS). However, the exact underlying mechanisms are still not completely understood. The nuclear receptor subfamily 4a (Nr4a) is a family of orphan nuclear receptors implicated in regulating MC activation, degranulation, cytokine/chemokine synthesis and release. Acute and chronic stress trigger hypothalamic–pituitaryadrenal axis (HPA) activation to induce the release of corticotropin-releasing hormone (CRH), resulting in MC activation and induction of the Nr4a family. Our newest data showed that Nr4a members were specially over-expressed in colonic MCs of the chronic water-avoidance stress (WAS)-induced visceral hyperalgesia mice, suggesting that Nr4a members might be involved in the pathophysiology of visceral hypersensitivity. In this review, we highlight the present knowledge on roles of Nr4a members in the activation of MCs and the pathophysiology of IBS, and discuss signaling pathways that modulate the activation of Nr4a family members. We propose that a better understanding of Nr4a members and their modulators may facilitate the development of more selective and effective therapies to treat IBS patients.http://www.sciencedirect.com/science/article/pii/S2001037022000575Mast cellsNuclear receptor subfamily 4aIrritable bowel syndromeHypothalamic–pituitaryadrenal axis |
| spellingShingle | Ruidi Li Shuhui Chen Xinpei Gu Shuhong An Zhaojin Wang Role of the nuclear receptor subfamily 4a in mast cells in the development of irritable bowel syndrome Computational and Structural Biotechnology Journal Mast cells Nuclear receptor subfamily 4a Irritable bowel syndrome Hypothalamic–pituitaryadrenal axis |
| title | Role of the nuclear receptor subfamily 4a in mast cells in the development of irritable bowel syndrome |
| title_full | Role of the nuclear receptor subfamily 4a in mast cells in the development of irritable bowel syndrome |
| title_fullStr | Role of the nuclear receptor subfamily 4a in mast cells in the development of irritable bowel syndrome |
| title_full_unstemmed | Role of the nuclear receptor subfamily 4a in mast cells in the development of irritable bowel syndrome |
| title_short | Role of the nuclear receptor subfamily 4a in mast cells in the development of irritable bowel syndrome |
| title_sort | role of the nuclear receptor subfamily 4a in mast cells in the development of irritable bowel syndrome |
| topic | Mast cells Nuclear receptor subfamily 4a Irritable bowel syndrome Hypothalamic–pituitaryadrenal axis |
| url | http://www.sciencedirect.com/science/article/pii/S2001037022000575 |
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