Revealing the Underlying Mechanism of Ischemia Reperfusion Injury Using Bioinformatics Approach

Shen, Bingbing; Zhou, Shan; He, Yue; Zhao, Hongwen; Mei, Mei; Wu, Xiongfei

doi:10.1159/000355759

Cited by 13 publications

(13 citation statements)

References 34 publications

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“…Study has found that the complement cascade plays a key role in numerous systemic organ IR models of tissue damage [25][26][27]. Shen et al [11] have also suggested that complement and coagulation cascades pathway is a significant pathway in IR injury. For the enriched DEG of C5, it has been suggested to play an important role in inflammatory and cell killing processes.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, kidney injury molecule-1 mRNA levels have been found elevated on the apical membrane of proximal tubular epithelial cells in most injured regions of the kidney [10]. Based on the dataset of GSE9943, Shen et al [11] revealed that miR-29c and transient receptor potential canonical (TRPC6) were potential novel targets for IR injury using bioinformatics approach. Although significant progress has been made to understand the potential significance of genetic factors in the kidney IR injury, relatively little is known about the molecular mechanisms responsible for the development and progression of kidney IR injury.…”

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confidence: 99%

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Identification of Genes and Pathways Associated with Kidney Ischemia-Reperfusion Injury by Bioinformatics Analyses

Wang

Tang²,

Ye³

et al. 2016

Kidney Blood Press Res

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Background/Aims: Ischemia-reperfusion (IR) injury in the kidney is a major cause of acute kidney injury in humans. However, the molecular mechanisms responsible for the progression of kidney IR injury still need to be explored. In this study, we aimed to explore the underlying genes and pathways associated with kidney IR injury. Methods: Gene microarray of GSE27274 was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between kidney IR injury and kidney IR rat samples were analyzed. Gene Ontology biological process (BP) and pathway enrichment analyses of DEGs were performed, followed by protein-protein interaction (PPI) network construction. Results: A total of 88 up-regulated and 102 down-regulated DEGs were identified. The up-regulated DEGs including FK506 binding protein 1A (Fkb1a) were mainly enriched in biological processes (BPs) related to protein ubiquitination. The down-regulated DEGs including complement component 5 (C5) were enriched in complement and coagulation cascades pathway. Choline phosphotransferase 1 (Chpt1) was enriched in glycerophospholipid metabolism pathway. In the PPI network, heme oxygenase (decycling) 1 (Hmox1) was as a hub gene that interacted with the maximum nodes. Conclusions: DEGs of Fkb1a, C5, Chpt1, and Hmox1, as well as complement and coagulation cascades pathway, glycerophospholipid metabolism pathway, and BP terms related to protein ubiquitinatione may be the potential targets for diagnosis and treatment of kidney IR injury.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Identification of Genes and Pathways Associated with Kidney Ischemia-Reperfusion Injury by Bioinformatics Analyses

Wang

Tang²,

Ye³

et al. 2016

Kidney Blood Press Res

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“…The mechanism of I/R injury may involve microvascular dysfunction, accumulation of oxygen free radicals, increased neutrophil activation and adhesion, release of inflammatory mediators (tumor necrosis factors [TNFs]), and the induction of cellular apoptosis . Neutrophils are commonly used for assessment of tissue damage caused by inflammatory factors during reperfusion .…”

Section: Introductionmentioning

confidence: 99%

“…2,39 The mechanism of I/R injury may involve microvascular dysfunction, accumulation of oxygen free radicals, increased neutrophil activation and adhesion, release of inflammatory mediators (tumor necrosis factors [TNFs]), and the induction of cellular apoptosis. 14,16,30 Neutrophils are commonly used for assessment of tissue damage caused by inflammatory factors during reperfusion. 21 Neutrophil infiltration into the tissue through a damaged vascular endothelial barrier is an important part of the development of I/R injury, and theoretically inhibiting neutrophil infiltration may reduce flap I/R injury.…”

Section: Introductionmentioning

confidence: 99%

Role of the p38 mitogen‐activated protein kinase signaling pathway in estrogen‐mediated protection following flap ischemia‐reperfusion injury

Hou

2016

Cell Biochemistry & Function

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Ischemia-reperfusion (I/R) injury often occurs during skin flap transplantation and results in tissue damage. Although estrogen treatment significantly alleviates this I/R injury-induced damage, the detailed molecular mechanism is not clear. In this study, a superficial epigastric artery flap I/R injury model was created in adult Wistar rats. Severe necrosis was observed in skin tissue after I/R injury. Histological examination of skin tissue revealed that I/R injury damages skin structure and results in neutrophil infiltration. Inflammation-related parameters, including neutrophil count, tumor necrosis factor-α, and interleukin-10 levels, were increased due to I/R injury. These pathological phenomena were reduced by estradiol treatment. Further investigation found that I/R injury triggers the p38 mitogen-activated protein kinase (p38-MAPK) pathway. The expression levels of p38-MAPK and phosphorylated p38-MAPK were increased after I/R injury. Estradiol increased the expression level of MAPK phosphatase-2, a putative phosphatase of p38, and reduced the levels of p38-MAPK and phosphorylated p38-MAPK. These results suggest that estradiol can improve skin flap survival, possibly by inhibiting neutrophil infiltration and the expression of p38-MAPK. This study provides an explanation for how estrogen alleviates I/R injury-induced damage that occurs during skin flap transplantation. In a rat pathological model, I/R injury leads to skin necrosis, skin structure damage, neutrophil infiltration, and inflammatory cytokine secretion, which are probably downstream effects of activation of the p38-MAPK pathway. On the other hand, estradiol treatment triggers the expression of MAPK phosphatase-2, a putative phosphatase of p38-MAPK, and reduced all examined pathological phenomena. Therefore, estrogen may reduce the deleterious effect of I/R injury on skin flap transplantation through modulating the p38-MAPK pathway.

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“…A number of studies have reported that I/R injury of skin flaps caused a series of complex pathophysiological processes mediated by various cell types and factors. The main mechanisms may involve the production of reactive oxygen species (ROS), the adhesion and aggregation of neutrophils, calcium overload, apoptosis and other processes (2)(3)(4)(5)(6). Apoptosis is considered to be an important factor in I/R injury of skin flaps (7).…”

Section: Introductionmentioning

confidence: 99%

Estradiol postconditioning relieves ischemia/reperfusion injury in axial skin flaps of rats, inhibits apoptosis and alters the MKP-1/ERK pathway

Jin

et al. 2017

Molecular Medicine Reports

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Previous studies have suggested that estradiol can reduce the ischemia/reperfusion (I/R) injury in skin flaps. However, the mechanism, particularly the signal pathways involved in this protective effect are not well established. In the current study, an I/R injury model was established in rats to explore the connection between estradiol protection during I/R injury and extracellular signal‑regulated kinase (ERK) signaling. Healthy male Wistar rats were divided into five groups (n=10): Control group (group I), I/R group (group II), saline group (group III), estradiol group (group IV) and inhibitor (PD‑98059) group (group V). The survival rate of the flap was compared between groups, morphological changes were observed by hematoxylin and eosin staining of sections, and terminal deoxynucleotidyl transferase dUTP nick end labeling was performed to identify apoptotic cells and determine the apoptotic index. To further investigate the mechanism, western blot analysis was performed to assess the protein level of ERK1/2, phospho‑ERK1/2, and mitogen‑activated protein kinase phosphatase 1 (MKP‑1). The results of the present study demonstrated that estradiol therapy can reduce I/R injury and decrease the apoptosis index in an axial skin flap model. The inhibitor of the ERK pathway (PD‑98059) partially abolished the effects of estradiol, which involve the phosphatase enzyme MKP‑1. Taken together, the findings of the present study indicate that estradiol may act by reducing the expression of MKP‑1, mediating the expression/activation changes of the ERK pathway and subsequently reduce the level of apoptosis and the I/R injury the axial flap. Estrogen may be used to mitigate the adverse reaction caused by ischemia‑reperfusion injury and effectively improve the survival rate and survival quality of free skin flap and improve patient prognosis.

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Revealing the Underlying Mechanism of Ischemia Reperfusion Injury Using Bioinformatics Approach

Cited by 13 publications

References 34 publications

Identification of Genes and Pathways Associated with Kidney Ischemia-Reperfusion Injury by Bioinformatics Analyses

Identification of Genes and Pathways Associated with Kidney Ischemia-Reperfusion Injury by Bioinformatics Analyses

Role of the p38 mitogen‐activated protein kinase signaling pathway in estrogen‐mediated protection following flap ischemia‐reperfusion injury

Estradiol postconditioning relieves ischemia/reperfusion injury in axial skin flaps of rats, inhibits apoptosis and alters the MKP-1/ERK pathway

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