Sorbitol Destroyed Intestinal Microfold Cells (M Cells) Development through Inhibition of PDE4-Mediated RANKL Expression
Objective. Microfold cells (M cells) are specific intestinal epithelial cells for monitoring and transcytosis of antigens, microorganisms, and pathogens in the intestine. However, the mechanism for M-cell development remained elusive. Materials and Methods. Real-time polymerase chain reaction, immun...
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| Format: | Article |
| Language: | English |
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Wiley
2024-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2024/7524314 |
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| _version_ | 1832553188376444928 |
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| author | Li Xiang Wenxu Pan Huan Chen Wenjun Du Shuping Xie Xinhua Liang Fangying Yang Rongwei Niu Canxin Huang Minan Luo Yuxin Xu Lanlan Geng Sitang Gong Wanfu Xu Junhong Zhao |
| author_facet | Li Xiang Wenxu Pan Huan Chen Wenjun Du Shuping Xie Xinhua Liang Fangying Yang Rongwei Niu Canxin Huang Minan Luo Yuxin Xu Lanlan Geng Sitang Gong Wanfu Xu Junhong Zhao |
| author_sort | Li Xiang |
| collection | DOAJ |
| description | Objective. Microfold cells (M cells) are specific intestinal epithelial cells for monitoring and transcytosis of antigens, microorganisms, and pathogens in the intestine. However, the mechanism for M-cell development remained elusive. Materials and Methods. Real-time polymerase chain reaction, immunofluorescence, and western blotting were performed to analyze the effect of sorbitol-regulated M-cell differentiation in vivo and in vitro, and luciferase and chromatin Immunoprecipitation were used to reveal the mechanism through which sorbitol-modulated M-cell differentiation. Results. Herein, in comparison to the mannitol group (control group), we found that intestinal M-cell development was inhibited in response to sorbitol treatment as evidenced by impaired enteroids accompanying with decreased early differentiation marker Annexin 5, Marcksl1, Spib, sox8, and mature M-cell marker glycoprotein 2 expression, which was attributed to downregulation of receptor activator of nuclear factor kappa-В ligand (RANKL) expression in vivo and in vitro. Mechanically, in the M-cell model, sorbitol stimulation caused a significant upregulation of phosphodiesterase 4 (PDE4) phosphorylation, leading to decreased protein kinase A (PKA)/cAMP-response element binding protein (CREB) activation, which further resulted in CREB retention in cytosolic and attenuated CREB binds to RANKL promoter to inhibit RANKL expression. Interestingly, endogenous PKA interacted with CREB, and this interaction was destroyed by sorbitol stimulation. Most importantly, inhibition of PDE4 by dipyridamole could rescue the inhibitory effect of sorbitol on intestinal enteroids and M-cell differentiation and mature in vivo and in vitro. Conclusion. These findings suggested that sorbitol suppressed intestinal enteroids and M-cell differentiation and matured through PDE4-mediated RANKL expression; targeting to inhibit PDE4 was sufficient to induce M-cell development. |
| format | Article |
| id | doaj-art-487c04afc8364221ba8876f52ba89ba9 |
| institution | Kabale University |
| issn | 1466-1861 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-487c04afc8364221ba8876f52ba89ba92025-02-03T05:54:35ZengWileyMediators of Inflammation1466-18612024-01-01202410.1155/2024/7524314Sorbitol Destroyed Intestinal Microfold Cells (M Cells) Development through Inhibition of PDE4-Mediated RANKL ExpressionLi Xiang0Wenxu Pan1Huan Chen2Wenjun Du3Shuping Xie4Xinhua Liang5Fangying Yang6Rongwei Niu7Canxin Huang8Minan Luo9Yuxin Xu10Lanlan Geng11Sitang Gong12Wanfu Xu13Junhong Zhao14Guangzhou Institute of PediatricsDepartment of GastroenterologyDepartment of GastroenterologyDepartment of GastroenterologyGuangzhou Institute of PediatricsDepartment of GastroenterologyDepartment of GastroenterologyThe First Affiliated Hospital of Jinan UniversityThe Second Clinical Medical SchoolThe School of PediatricsGuangzhou Institute of PediatricsGuangzhou Institute of PediatricsGuangzhou Institute of PediatricsGuangzhou Institute of PediatricsDepartment of GastroenterologyObjective. Microfold cells (M cells) are specific intestinal epithelial cells for monitoring and transcytosis of antigens, microorganisms, and pathogens in the intestine. However, the mechanism for M-cell development remained elusive. Materials and Methods. Real-time polymerase chain reaction, immunofluorescence, and western blotting were performed to analyze the effect of sorbitol-regulated M-cell differentiation in vivo and in vitro, and luciferase and chromatin Immunoprecipitation were used to reveal the mechanism through which sorbitol-modulated M-cell differentiation. Results. Herein, in comparison to the mannitol group (control group), we found that intestinal M-cell development was inhibited in response to sorbitol treatment as evidenced by impaired enteroids accompanying with decreased early differentiation marker Annexin 5, Marcksl1, Spib, sox8, and mature M-cell marker glycoprotein 2 expression, which was attributed to downregulation of receptor activator of nuclear factor kappa-В ligand (RANKL) expression in vivo and in vitro. Mechanically, in the M-cell model, sorbitol stimulation caused a significant upregulation of phosphodiesterase 4 (PDE4) phosphorylation, leading to decreased protein kinase A (PKA)/cAMP-response element binding protein (CREB) activation, which further resulted in CREB retention in cytosolic and attenuated CREB binds to RANKL promoter to inhibit RANKL expression. Interestingly, endogenous PKA interacted with CREB, and this interaction was destroyed by sorbitol stimulation. Most importantly, inhibition of PDE4 by dipyridamole could rescue the inhibitory effect of sorbitol on intestinal enteroids and M-cell differentiation and mature in vivo and in vitro. Conclusion. These findings suggested that sorbitol suppressed intestinal enteroids and M-cell differentiation and matured through PDE4-mediated RANKL expression; targeting to inhibit PDE4 was sufficient to induce M-cell development.http://dx.doi.org/10.1155/2024/7524314 |
| spellingShingle | Li Xiang Wenxu Pan Huan Chen Wenjun Du Shuping Xie Xinhua Liang Fangying Yang Rongwei Niu Canxin Huang Minan Luo Yuxin Xu Lanlan Geng Sitang Gong Wanfu Xu Junhong Zhao Sorbitol Destroyed Intestinal Microfold Cells (M Cells) Development through Inhibition of PDE4-Mediated RANKL Expression Mediators of Inflammation |
| title | Sorbitol Destroyed Intestinal Microfold Cells (M Cells) Development through Inhibition of PDE4-Mediated RANKL Expression |
| title_full | Sorbitol Destroyed Intestinal Microfold Cells (M Cells) Development through Inhibition of PDE4-Mediated RANKL Expression |
| title_fullStr | Sorbitol Destroyed Intestinal Microfold Cells (M Cells) Development through Inhibition of PDE4-Mediated RANKL Expression |
| title_full_unstemmed | Sorbitol Destroyed Intestinal Microfold Cells (M Cells) Development through Inhibition of PDE4-Mediated RANKL Expression |
| title_short | Sorbitol Destroyed Intestinal Microfold Cells (M Cells) Development through Inhibition of PDE4-Mediated RANKL Expression |
| title_sort | sorbitol destroyed intestinal microfold cells m cells development through inhibition of pde4 mediated rankl expression |
| url | http://dx.doi.org/10.1155/2024/7524314 |
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