Nateglinide Exerts Neuroprotective Effects via Downregulation of HIF-1α/TIM-3 Inflammatory Pathway and Promotion of Caveolin-1 Expression in the Rat’s Hippocampus Subjected to Focal Cerebral Ischemia/Reperfusion Injury

Saad, Marina; Fahmy, Mohamed Ibrahim Mohamed; Al-Shorbagy, Muhammad Y.; Assaf, Naglaa; Hegazy, Ahmed; El-Yamany, Mohammed F.

doi:10.1007/s10753-019-01154-3

Cited by 14 publications

(6 citation statements)

References 63 publications

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“…It causes approximately 4.4 million deaths each year and treating patients who have suffered a stroke generates between $59 and $230 thousand dollars in health care expenses per patient, putting severe economic burdens on patients, families, and national health services [4]. Ischemic stroke is a multi-factorial disease associated with inflammation, apoptosis, and oxidative stress responses [5]. The subsequent oxidative stress that follows ischemic stroke causes neuronal death, damage to the blood-brain barrier, neurovascular injury, edema and bleeding [6].…”

Section: Introductionmentioning

confidence: 99%

miR-137 prevents inflammatory response, oxidative stress, neuronal injury and cognitive impairment via blockade of Src-mediated MAPK signaling pathway in ischemic stroke

Tian

et al. 2020

Aging

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Stroke is a leading cause of death and disability worldwide. The purpose of this study was to investigate the possible role of the microRNA (miRNA or miR) miR-137 in ischemic stroke. miRNAs are very stable in the blood and may serve as potential diagnostic and therapeutic markers. Wild-type, Src-/and miR-137-/mice were treated with p38 siRNA or Erk2 siRNA to identify their roles in the inflammatory response, oxidative stress, neuronal injury and cognitive impairment in brain tissues of mice following middle cerebral artery occlusion (MCAO) operation. We evaluated several factors including; inflammatory responses, oxidative stress, viability and apoptosis of astrocytes in order to identify the functions of miR-137 and Src in ischemic stroke. miR-137 alleviated the inflammatory response, oxidative stress, neuronal injury and cognitive impairment, and restricted apoptosis via targeting Src and inactivating the MAPK signaling pathway. Furthermore, up-regulation of miR-137 or inhibition of Src inhibited the secretion of inflammatory factors, suppressed oxidative stress, and reduced apoptosis of astrocytes. In conclusion, our work suggests that, in mice, miR-137 confers neuroprotective effects against ischemic stroke via attenuation of oxidative, apoptotic, and inflammatory pathways through inhibiting Src-dependent MAPK signaling pathway.

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Section: Introductionmentioning

confidence: 99%

miR-137 prevents inflammatory response, oxidative stress, neuronal injury and cognitive impairment via blockade of Src-mediated MAPK signaling pathway in ischemic stroke

Tian

et al. 2020

Aging

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“…Abnormal Tim-3 expression can be detected on the surface of renal parenchymal cells or immune cells in IgA nephropathy [43], lupus nephritis [44], diabetic nephropathy [45], renal tumor [46], and renal transplantation rejection [47]. Tim-3 also participates in the pathogenesis of liver IRI [26,38,40], brain IRI [48,49], and lung IRI [21]. The activation of the Gal-9/Tim-3 signaling pathway has a protective effect on liver IRI via negative regulation [38].…”

Section: Discussionmentioning

confidence: 99%

Gal-9/Tim-3 signaling pathway activation suppresses the generation of Th17 cells and promotes the induction of Foxp3+regulatory T cells in renal ischemia-reperfusion injury

Tao

WANG

Feng

et al. 2022

Preprint

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CD4+T cells mediate the pathogenesis of renal ischemia-reperfusion injury (IRI). Emerging research suggests that a Th17/regulatory T cell (Treg) imbalance plays a pivotal role in the development of renal IRI. The recently identified negative checkpoint T cell immunoglobulin domain and mucin domain family 3 (Tim-3) inhibits the immune response by binding to its ligand, galectin-9 (Gal-9). However, the role of the Gal-9/Tim-3 signaling pathway in the regulation of CD4+T cell subsets in renal IRI remains unclear. In this study, the effect of the Gal-9/Tim-3 signaling pathway on Th17/Treg subsets in renal IRI was investigated using a mouse model. Renal IRI induced the expression of Gal-9 in renal tubular epithelial cells and increased the percentages of Tim-3+Th17 cells and Tim-3+Foxp3+Treg cells in the IR kidneys. The administration of rAAV9-Gal-9 suppressed kidney inflammation, reduced the mortality of mice with renal IRI, increased Foxp3+Treg cells, and reduced Th17 cells. In contrast, the blockade of Tim-3 in vivo with an anti-Tim-3 mAb aggravated renal inflammation, decreased Foxp3+Treg cells, and promoted Th17 cells. Thus, Gal-9/Tim-3 signaling pathway activation may protect against renal IRI by inhibiting Th17 cell production and inducing Foxp3+Treg cell expansion. Our study suggests that the Gal-9/Tim-3 signaling pathway might become a target of immunotherapy in renal IRI.

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“…Curcumin exerts a neuroprotective effect by inhibiting the interaction between HIF-1α and autophagy in cerebral I/R injury ( 128 ). A recent study has reported that nateglinide stabilizes HIF-1 cerebral I/R injury by inhibiting STAT-3 phosphorylation and stops the expression of HIF-1α-dependent inflammation and mediators of apoptosis, namely phorbol-12-myristate-13-acetate-induced protein 1 and NF-κB ( 129 ). Different drugs have a neuroprotective effect through the opposite regulation of HIF-1α, which may be due to the different mechanisms of HIF-1α in the neuroprotective effect of cerebral ischemia.…”

Section: Role Of Hif-1α In the Protective Effects Of Natural Compounds Against Cerebral Ischemiamentioning

confidence: 99%

HIF‑1α in cerebral ischemia (Review)

Dong

Han

2021

Mol Med Rep

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Cerebral ischemic injury may lead to a series of serious brain diseases, death or different degrees of disability. Hypoxia-inducible factor-1α (HIF-1α) is an oxygen-sensitive transcription factor, which mediates the adaptive metabolic response to hypoxia and serves a key role in cerebral ischemia. HIF-1α is the main molecule that responds to hypoxia. HIF-1α serves an important role in the development of cerebral ischemia by participating in numerous processes, including metabolism, proliferation and angiogenesis. The present review focuses on the endogenous protective mechanism of cerebral ischemia and elaborates on the role of HIF-1α in cerebral ischemia. In addition, it focuses on cerebral ischemia interventions that act on the HIF-1α target, including biological factors, non-coding RNA, hypoxic-ischemic preconditioning and drugs, and expands upon the measures to strengthen the endogenous compensatory response to support HIF-1α as a therapeutic target, thus providing novel suggestions for the treatment of cerebral ischemia. Contents1. Introduction 2. Literature screening method 3. Role of HIF-1α in cerebral ischemia 4. HIF-1α protects the brain via the regulation of endogenous substances 5. Role of HIF-1α in cerebral ischemic preconditioning (IPC) 6. Role of HIF-1α in the protective effects of natural compounds against cerebral ischemia 7. Concluding remarks and future perspectives

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Nateglinide Exerts Neuroprotective Effects via Downregulation of HIF-1α/TIM-3 Inflammatory Pathway and Promotion of Caveolin-1 Expression in the Rat’s Hippocampus Subjected to Focal Cerebral Ischemia/Reperfusion Injury

Cited by 14 publications

References 63 publications

miR-137 prevents inflammatory response, oxidative stress, neuronal injury and cognitive impairment via blockade of Src-mediated MAPK signaling pathway in ischemic stroke

miR-137 prevents inflammatory response, oxidative stress, neuronal injury and cognitive impairment via blockade of Src-mediated MAPK signaling pathway in ischemic stroke

Gal-9/Tim-3 signaling pathway activation suppresses the generation of Th17 cells and promotes the induction of Foxp3+regulatory T cells in renal ischemia-reperfusion injury

HIF‑1α in cerebral ischemia (Review)

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