Chitinase 3‐like 1 overexpression aggravates hypoxia–reoxygenation injury in IEC‐6 cells by inhibiting the PI3K/AKT signalling pathway
Abstract Intestinal ischaemia–reperfusion (I/R) is a common clinical pathology with high incidence and mortality rates. However, the mechanisms underlying intestinal I/R injury remain unclear. In this study, we investigated the role and mechanism of chitinase 3‐like 1 (CHI3L1) during intestinal I/R...
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| Format: | Article |
| Language: | English |
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Wiley
2024-12-01
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| Series: | Experimental Physiology |
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| Online Access: | https://doi.org/10.1113/EP091768 |
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| author | Lei Mi Jie Jin Yingying Zhang Ming Chen JianLi Cui Rui Chen Xiao Zheng Changqing Jing |
| author_facet | Lei Mi Jie Jin Yingying Zhang Ming Chen JianLi Cui Rui Chen Xiao Zheng Changqing Jing |
| author_sort | Lei Mi |
| collection | DOAJ |
| description | Abstract Intestinal ischaemia–reperfusion (I/R) is a common clinical pathology with high incidence and mortality rates. However, the mechanisms underlying intestinal I/R injury remain unclear. In this study, we investigated the role and mechanism of chitinase 3‐like 1 (CHI3L1) during intestinal I/R injury. Therefore, we analysed the expression levels of CHI3L1 in the intestinal tissue of an intestinal I/R rat model and explored its effects and mechanism in a hypoxia–reoxygenation (H/R) IEC‐6 cell model. We found that intestinal I/R injury elevated CHI3L1 levels in the serum, ileum and duodenum, whereas H/R enhanced CHI3L1 expression in IEC‐6 cells. The H/R‐induced inhibition of proliferation and apoptosis was alleviated by CHI3L1 knockdown and aggravated by CHI3L1 overexpression. In addition, CHI3L1 knockdown alleviated, and CHI3L1 overexpression aggravated, the H/R‐induced inflammatory response and oxidative stress. Mechanistically, CHI3L1 overexpression weakened the activation of the phosphoinositide 3‐kinase (PI3K)/AKT pathway, suppressed the nuclear translocation of Nrf2, and promoted the nuclear translocation of nuclear factor κB (NF‐κB). Moreover, CHI3L1 knockdown had the opposite effect on the PI3K/AKT pathway, Nrf2, and NF‐κB. Moreover, the PI3K inhibitor LY294002 blocked the effect of CHI3L1 knockdown on the H/R‐induced inhibition of proliferation, apoptosis, inflammatory response and oxidative stress. In conclusion, CHI3L1 expression was induced during intestinal I/R and H/R injury in IEC‐6 cells, and CHI3L1 overexpression aggravated H/R injury in IEC‐6 cells by inhibiting the PI3K/AKT signalling pathway. Therefore, CHI3L1 may be an effective target for controlling intestinal I/R injury. |
| format | Article |
| id | doaj-art-a67fd2466fe74b259c3c951f3d394618 |
| institution | Kabale University |
| issn | 0958-0670 1469-445X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Experimental Physiology |
| spelling | doaj-art-a67fd2466fe74b259c3c951f3d3946182024-11-30T11:02:31ZengWileyExperimental Physiology0958-06701469-445X2024-12-01109122073208710.1113/EP091768Chitinase 3‐like 1 overexpression aggravates hypoxia–reoxygenation injury in IEC‐6 cells by inhibiting the PI3K/AKT signalling pathwayLei Mi0Jie Jin1Yingying Zhang2Ming Chen3JianLi Cui4Rui Chen5Xiao Zheng6Changqing Jing7Department of Gastrointestinal Surgery The Affiliated Taian City Central Hospital of Qingdao University Tai'an ChinaDepartment of Traditional Chinese Medicine The Affiliated Taian City Central Hospital of Qingdao University Tai'an ChinaDepartment of Gastrointestinal Surgery The Affiliated Taian City Central Hospital of Qingdao University Tai'an ChinaDepartment of Gastrointestinal Surgery The Affiliated Taian City Central Hospital of Qingdao University Tai'an ChinaDepartment of Gastrointestinal Surgery The Affiliated Taian City Central Hospital of Qingdao University Tai'an ChinaDepartment of Gastrointestinal Surgery The Affiliated Taian City Central Hospital of Qingdao University Tai'an ChinaDepartment of Gastrointestinal Surgery The Affiliated Taian City Central Hospital of Qingdao University Tai'an ChinaDepartment of Gastrointestinal Surgery Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan ChinaAbstract Intestinal ischaemia–reperfusion (I/R) is a common clinical pathology with high incidence and mortality rates. However, the mechanisms underlying intestinal I/R injury remain unclear. In this study, we investigated the role and mechanism of chitinase 3‐like 1 (CHI3L1) during intestinal I/R injury. Therefore, we analysed the expression levels of CHI3L1 in the intestinal tissue of an intestinal I/R rat model and explored its effects and mechanism in a hypoxia–reoxygenation (H/R) IEC‐6 cell model. We found that intestinal I/R injury elevated CHI3L1 levels in the serum, ileum and duodenum, whereas H/R enhanced CHI3L1 expression in IEC‐6 cells. The H/R‐induced inhibition of proliferation and apoptosis was alleviated by CHI3L1 knockdown and aggravated by CHI3L1 overexpression. In addition, CHI3L1 knockdown alleviated, and CHI3L1 overexpression aggravated, the H/R‐induced inflammatory response and oxidative stress. Mechanistically, CHI3L1 overexpression weakened the activation of the phosphoinositide 3‐kinase (PI3K)/AKT pathway, suppressed the nuclear translocation of Nrf2, and promoted the nuclear translocation of nuclear factor κB (NF‐κB). Moreover, CHI3L1 knockdown had the opposite effect on the PI3K/AKT pathway, Nrf2, and NF‐κB. Moreover, the PI3K inhibitor LY294002 blocked the effect of CHI3L1 knockdown on the H/R‐induced inhibition of proliferation, apoptosis, inflammatory response and oxidative stress. In conclusion, CHI3L1 expression was induced during intestinal I/R and H/R injury in IEC‐6 cells, and CHI3L1 overexpression aggravated H/R injury in IEC‐6 cells by inhibiting the PI3K/AKT signalling pathway. Therefore, CHI3L1 may be an effective target for controlling intestinal I/R injury.https://doi.org/10.1113/EP091768CHI3L1intestinal ischaemia–reperfusionNF‐κBNrf2nuclear translocationPI3K/AKT |
| spellingShingle | Lei Mi Jie Jin Yingying Zhang Ming Chen JianLi Cui Rui Chen Xiao Zheng Changqing Jing Chitinase 3‐like 1 overexpression aggravates hypoxia–reoxygenation injury in IEC‐6 cells by inhibiting the PI3K/AKT signalling pathway Experimental Physiology CHI3L1 intestinal ischaemia–reperfusion NF‐κB Nrf2 nuclear translocation PI3K/AKT |
| title | Chitinase 3‐like 1 overexpression aggravates hypoxia–reoxygenation injury in IEC‐6 cells by inhibiting the PI3K/AKT signalling pathway |
| title_full | Chitinase 3‐like 1 overexpression aggravates hypoxia–reoxygenation injury in IEC‐6 cells by inhibiting the PI3K/AKT signalling pathway |
| title_fullStr | Chitinase 3‐like 1 overexpression aggravates hypoxia–reoxygenation injury in IEC‐6 cells by inhibiting the PI3K/AKT signalling pathway |
| title_full_unstemmed | Chitinase 3‐like 1 overexpression aggravates hypoxia–reoxygenation injury in IEC‐6 cells by inhibiting the PI3K/AKT signalling pathway |
| title_short | Chitinase 3‐like 1 overexpression aggravates hypoxia–reoxygenation injury in IEC‐6 cells by inhibiting the PI3K/AKT signalling pathway |
| title_sort | chitinase 3 like 1 overexpression aggravates hypoxia reoxygenation injury in iec 6 cells by inhibiting the pi3k akt signalling pathway |
| topic | CHI3L1 intestinal ischaemia–reperfusion NF‐κB Nrf2 nuclear translocation PI3K/AKT |
| url | https://doi.org/10.1113/EP091768 |
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