Expression of p38 mitogen‐activated protein kinase (p38MAPK) and pathological change in intussusception

Guo, Wang; Wang, Jian; Liu, Chi; Yang, Fu-bin; Li, Shaowei

doi:10.1111/ped.12928

Cited by 4 publications

(7 citation statements)

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“…Growing evidence demonstrates that the p38MAPK family plays an important role in intracellular signal transduction in response to extracellular stimuli, including intestinal I/R challenge (Fu, Xing, et al, 2003;Fu, Yang, et al, 2003;Guo et al, 2016;Li et al, 2021;Li, Xu, et al, 2017;Liu et al, 2020;Ming et al, 2019;Murayama et al, 2006;Santén et al, 2009;Yusof et al, 2009;Zheng et al, 2005). Dexmedetomidine (Liu et al, 2020), propofol (Li et al, 2021), and 6-gingerol (Li, Xu, et al, 2017) have been shown to protect against intestinal I/R injury via p38MAPK inhibition, wherein p38MAPK activation conferred detrimental effects on intestinal I/R progression.…”

Section: Discussionmentioning

confidence: 99%

Remifentanil Promotes PDIA3 Expression by Activating p38MAPK to Inhibit Intestinal Ischemia/Reperfusion-Induced Oxidative and Endoplasmic Reticulum Stress

Shen

Zhan

et al. 2022

Front. Cell Dev. Biol.

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Background: Remifentanil protects against intestinal ischemia/reperfusion (I/R) injury; however, its exact mechanism remains to be elucidated. The objective of this study was to investigate the underlying molecular mechanism of remifentanil in intestinal I/R injury in mice.Methods: We evaluated the intestine-protective effect of remifentanil in adult male mice with 45 min superior mesenteric artery occlusion followed by 4 h reperfusion by determining the following: intestinal Chiu’s scores, diamine oxidase, and intestinal fatty acid binding protein in serum; the apoptotic index, lipid peroxidation product malondialdehyde (MDA), and superoxide dismutase (SOD) activity in the intestinal mucosa; and the intestinal mRNA and protein expressions of Bip, CHOP, caspase-12, and cleaved caspase-3, reflecting endoplasmic reticulum (ER) stress. Furthermore, conditional knockout mice, in which the protein disulfide isomerase A3 (PDIA3) gene was deleted from the intestinal epithelium, and SB203580 (a selective p38MAPK inhibitor) were used to determine the role of PDIA3 and p38MAPK in I/R progression and intestinal protection by remifentanil.Results: Our data showed that intestinal I/R induced obvious oxidative stress and endoplasmic reticulum stress–related cell apoptosis, as evidenced by an increase in the intestinal mucosal malondialdehyde, a decrease in the intestinal mucosal SOD, and an increase in the apoptotic index and the mRNA and protein expression of Bip, CHOP, caspase-12, and cleaved caspase-3. Remifentanil significantly improved these changes. Moreover, the deletion of intestinal epithelium PDIA3 blocked the protective effects of remifentanil. SB203580 also abolished the intestinal protection of remifentanil and downregulated the mRNA and protein expression of PDIA3.Conclusion: Remifentanil appears to act via p38MAPK to protect the small intestine from intestinal I/R injury by its PDIA3-mediated antioxidant and anti-ER stress properties.

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Section: Discussionmentioning

confidence: 99%

Remifentanil Promotes PDIA3 Expression by Activating p38MAPK to Inhibit Intestinal Ischemia/Reperfusion-Induced Oxidative and Endoplasmic Reticulum Stress

Shen

Zhan

et al. 2022

Front. Cell Dev. Biol.

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“…Previous studies have demonstrated that TLR4 can activate the MAPK and NF-kB pathways, which are critical regulators of the inflammatory response, cell survival, and apoptosis [ 3 ]. We previously observed high p38 MAPK expression in response to I/R injury [ 18 ]. Additionally, Ben et al demonstrated that TLR4 plays an important role in acute lung injury following intestinal ischemia [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

“…TAK-242 (3 mg/kg), a specific inhibitor of TLR4, was administered intraperitoneally 60 min prior to intussusception. Intussusception was established under ether inhalation anesthesia as described previously [ 18 ]. Intussusception was observed in all mice in the I/R injury and TAK-242 groups after 60 min.…”

Section: Methodsmentioning

confidence: 99%

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Molecular imaging of Toll-like receptor 4 detects ischemia-reperfusion injury during intussusception

Tan

Shungen

et al. 2017

Oncotarget

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We investigated the expression of Toll-like receptor 4 (TLR4) in the acute phase of intestinal I/R injury during intussusception and evaluated whether anti-TLR4 antibody-conjugated lead sulfide quantum dots (TLR4-PbS QDs) could be used to detect and monitor the injury. We first established a mouse model of I/R injury during intussusception. TLR-PbS QDs were then intravenously administered to intestinal I/R injured mice and visualized using whole-body fluorescence imaging in the second near-infrared window (NIR-II). Immunohistochemical analysis of intestinal tissue from the mice revealed that TLR4 expression was higher in the I/R injury group than the control and TAK-242 groups (5.189 ± 2.482, 1.186 ± 1.171, and 2.400 ± 0.857, respectively, P < 0.05). NIR-II fluorescence intensity was also higher in the I/R injury group than in the control and TAK-242 groups (86.415 ± 10.955, 38.975 ± 8.619, and 71.977 ± 3.838, respectively; P < 0.05). Thus, anti-TLR4-PbS QDs bound to TLR4 on the cell membranes of intestinal epithelial cells with high specificity in vitro and in vivo. These results indicate that TLR4 promotes intestinal I/R injury during intussusception and that the injury can be noninvasively imaged using TLR4-PbS QDs.

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“…Intestinal ischemia-reperfusion injury (I/R) can occur during pediatric intussusception [3,4], and any delay in diagnosis or treatment can lead to loss of intestinal viability that requires bowel resection [5,6].…”

Section: Introductionmentioning

confidence: 99%

Serum tRNA-Derived Fragments as Potential Biomarkers in Children with Acute Intussusception

Chen

Zhao

Guo

2020

Preprint

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Background: The aim of the present study was to investigate whether transfer ribonucleic acid (tRNA)–derived fragments (tRFs) can serve as candidate biomarkers for pediatric intussusception.Methods: Using high-throughput sequencing technology, we identified differentially expressed tRFs, and ultimately selected three tRFs to establish a signature as a predictive biomarker of pediatric intussusception. Selection of these three upregulated genes was veriﬁed using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). We conducted receiver operator characteristic (ROC) curve analysis to evaluate the predictive accuracy of the selected genes for pediatric intussusception.Results: We detected 732 tRFs and tRNA-derived stress-induced RNA (tiRNAs), 1705 micro-RNAs (miRNAs), 52 differentially expressed miRNAs, and 34 differentially expressed tRFs and tiRNAs between patients and controls. Compared with controls, we found 33 upregulated miRNAs, 24 upregulated tRFs and tiRNAs, 19 downregulated miRNAs, and 10 downregulated tRFs and tiRNAs in children with intussusception. Using qPCR, the expression trends of tRF-Leu-TAA-006, tRF-Gln-TTG-033 and tRF-Lys-TTT-028 were consistent with the sequencing results. AUCs of tRF-Leu-TAA-006, tRF-Gln-TTG-033 and tRF-Lys-TTT-028 were 0.984, 0.970 and 0.837, respectively.Conclusion: Circulating tRF-Leu-TAA-006, tRF-Gln-TTG-033 and tRF-Lys-TTT-028 expression might be a novel potential biomarker for diagnosis of pediatric intussusception.

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Expression of p38 mitogen‐activated protein kinase (p38MAPK) and pathological change in intussusception

Abstract: The present mouse model can be used to assess the dynamic pathological changes associated with intussusception. I/R is associated with upregulation of p38MAPK in intussusception.

Cited by 4 publications

References 26 publications

Remifentanil Promotes PDIA3 Expression by Activating p38MAPK to Inhibit Intestinal Ischemia/Reperfusion-Induced Oxidative and Endoplasmic Reticulum Stress

Remifentanil Promotes PDIA3 Expression by Activating p38MAPK to Inhibit Intestinal Ischemia/Reperfusion-Induced Oxidative and Endoplasmic Reticulum Stress

Molecular imaging of Toll-like receptor 4 detects ischemia-reperfusion injury during intussusception

Serum tRNA-Derived Fragments as Potential Biomarkers in Children with Acute Intussusception

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