miR-199a-5p Exacerbated Intestinal Barrier Dysfunction through Inhibiting Surfactant Protein D and Activating NF-κB Pathway in Sepsis
Sepsis is a severe disease, which results from the excessive inflammatory response to the infection. Dysfunction of intestinal barrier is a crucial problem in various pathological conditions. Meanwhile, microRNAs exhibit significant roles in the modulation of many diseases, including sepsis. Multipl...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2020/8275026 |
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| author | Xianjin Du Dan Tian Jie Wei Chen Yan Peng Hu Xu Wu Wenbin Yang Zhanyong Zhu |
| author_facet | Xianjin Du Dan Tian Jie Wei Chen Yan Peng Hu Xu Wu Wenbin Yang Zhanyong Zhu |
| author_sort | Xianjin Du |
| collection | DOAJ |
| description | Sepsis is a severe disease, which results from the excessive inflammatory response to the infection. Dysfunction of intestinal barrier is a crucial problem in various pathological conditions. Meanwhile, microRNAs exhibit significant roles in the modulation of many diseases, including sepsis. Multiple investigations indicate that miR-199a-5p participates in different human diseases. Nevertheless, little is known on the roles of miR-199a-5p in sepsis. Herein, we evaluated the mechanism of miR-199a-5p on the intestinal barrier dysfunction in sepsis. Intestinal mucosa permeability indicators including D-lactic acid, DAO, and FD-40 levels were determined, and they were greatly increased in sepsis. Then, we proved that miR-199a-5p was induced in sepsis mice tissues and isolated intestinal epithelial cells. Moreover, miR-199a-5p increased D-lactic acid, DAO, and FD-40 while inhibition of miR-199a-5p exhibited a reversed process. Additionally, we observed that miR-199a-5p affected the oxidative damage and inflammation in the intestine tissues from sepsis mice. The content of MDA was elevated whereas SOD was remarkably repressed in the miR-199a-5p mimic group. IL-6, IL-1β, and TNF-α were induced by miR-199a-5p overexpression while IL-10 was reduced by miR-199a-5p. Subsequently, surfactant protein D (SP-D) was predicted as the target of miR-199a-5p. The activation of NF-κB has been identified in sepsis. Herein, we demonstrated that inhibitor of miR-199a-5p contributed to IEC injury via targeting SP-D and inactivating the NF-κB pathway. These revealed miR-199a-5p exacerbated the intestinal barrier dysfunction via inhibiting SP-D and activating the NF-κB pathway in sepsis. |
| format | Article |
| id | doaj-art-7d922a29ec474cdebfe1a8d9b704f812 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-7d922a29ec474cdebfe1a8d9b704f8122025-02-03T01:05:02ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/82750268275026miR-199a-5p Exacerbated Intestinal Barrier Dysfunction through Inhibiting Surfactant Protein D and Activating NF-κB Pathway in SepsisXianjin Du0Dan Tian1Jie Wei2Chen Yan3Peng Hu4Xu Wu5Wenbin Yang6Zhanyong Zhu7Department of Emergency, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, ChinaDepartment of Emergency, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, ChinaDepartment of Emergency, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, ChinaDepartment of Emergency, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, ChinaDepartment of Emergency, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, ChinaDepartment of Emergency, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, ChinaDepartment of Emergency, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, ChinaDepartment of Plastic Surgery, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan, Hubei 430060, ChinaSepsis is a severe disease, which results from the excessive inflammatory response to the infection. Dysfunction of intestinal barrier is a crucial problem in various pathological conditions. Meanwhile, microRNAs exhibit significant roles in the modulation of many diseases, including sepsis. Multiple investigations indicate that miR-199a-5p participates in different human diseases. Nevertheless, little is known on the roles of miR-199a-5p in sepsis. Herein, we evaluated the mechanism of miR-199a-5p on the intestinal barrier dysfunction in sepsis. Intestinal mucosa permeability indicators including D-lactic acid, DAO, and FD-40 levels were determined, and they were greatly increased in sepsis. Then, we proved that miR-199a-5p was induced in sepsis mice tissues and isolated intestinal epithelial cells. Moreover, miR-199a-5p increased D-lactic acid, DAO, and FD-40 while inhibition of miR-199a-5p exhibited a reversed process. Additionally, we observed that miR-199a-5p affected the oxidative damage and inflammation in the intestine tissues from sepsis mice. The content of MDA was elevated whereas SOD was remarkably repressed in the miR-199a-5p mimic group. IL-6, IL-1β, and TNF-α were induced by miR-199a-5p overexpression while IL-10 was reduced by miR-199a-5p. Subsequently, surfactant protein D (SP-D) was predicted as the target of miR-199a-5p. The activation of NF-κB has been identified in sepsis. Herein, we demonstrated that inhibitor of miR-199a-5p contributed to IEC injury via targeting SP-D and inactivating the NF-κB pathway. These revealed miR-199a-5p exacerbated the intestinal barrier dysfunction via inhibiting SP-D and activating the NF-κB pathway in sepsis.http://dx.doi.org/10.1155/2020/8275026 |
| spellingShingle | Xianjin Du Dan Tian Jie Wei Chen Yan Peng Hu Xu Wu Wenbin Yang Zhanyong Zhu miR-199a-5p Exacerbated Intestinal Barrier Dysfunction through Inhibiting Surfactant Protein D and Activating NF-κB Pathway in Sepsis Mediators of Inflammation |
| title | miR-199a-5p Exacerbated Intestinal Barrier Dysfunction through Inhibiting Surfactant Protein D and Activating NF-κB Pathway in Sepsis |
| title_full | miR-199a-5p Exacerbated Intestinal Barrier Dysfunction through Inhibiting Surfactant Protein D and Activating NF-κB Pathway in Sepsis |
| title_fullStr | miR-199a-5p Exacerbated Intestinal Barrier Dysfunction through Inhibiting Surfactant Protein D and Activating NF-κB Pathway in Sepsis |
| title_full_unstemmed | miR-199a-5p Exacerbated Intestinal Barrier Dysfunction through Inhibiting Surfactant Protein D and Activating NF-κB Pathway in Sepsis |
| title_short | miR-199a-5p Exacerbated Intestinal Barrier Dysfunction through Inhibiting Surfactant Protein D and Activating NF-κB Pathway in Sepsis |
| title_sort | mir 199a 5p exacerbated intestinal barrier dysfunction through inhibiting surfactant protein d and activating nf κb pathway in sepsis |
| url | http://dx.doi.org/10.1155/2020/8275026 |
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