Epac-1/Rap-1 signaling pathway orchestrates the reno-therapeutic effect of ticagrelor against renal ischemia/reperfusion model

El-Mokadem, Bassant M.; El‐Abhar, Hanan S.; Abdallah, Dalaal M.; Awad, Azza S.; Soubh, Ayman A.

doi:10.1016/j.biopha.2021.111488

Cited by 14 publications

(13 citation statements)

References 59 publications

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“…Ischemic kidney disease causes irreversible damage to the renal structure, leading to renal failure. Epac signaling is found to protect renal function by activating downstream molecules, especially Rap1 signaling ( Stokman et al, 2011 ; Stokman et al, 2014 ; El-Mokadem et al, 2021 ). Endothelial progenitor cells (EPCs) can protect the kidneys in a mouse model of acute ischemic renal failure.…”

Section: Kidney Diseasesmentioning

confidence: 99%

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Epac: A Promising Therapeutic Target for Vascular Diseases: A Review

et al. 2022

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Vascular diseases affect the circulatory system and comprise most human diseases. They cause severe symptoms and affect the quality of life of patients. Recently, since their identification, exchange proteins directly activated by cAMP (Epac) have attracted increasing scientific interest, because of their role in cyclic adenosine monophosphate (cAMP) signaling, a well-known signal transduction pathway. The role of Epac in cardiovascular disease and cancer is extensively studied, whereas their role in kidney disease has not been comprehensively explored yet. In this study, we aimed to review recent studies on the regulatory effects of Epac on various vascular diseases, such as cardiovascular disease, cerebrovascular disease, and cancer. Accumulating evidence has shown that both Epac1 and Epac2 play important roles in vascular diseases under both physiological and pathological conditions. Additionally, there has been an increasing focus on Epac pharmacological modulators. Therefore, we speculated that Epac could serve as a novel therapeutic target for the treatment of vascular diseases.

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Section: Kidney Diseasesmentioning

confidence: 99%

“…In summary, 8CPT and 8CPT-AM are the two main activators of Epac. Moreover, in addition to 8CPT and 8CPT-AM, ticagrelor also can activate the Epac1/Rap1 signaling pathway ( El-Mokadem et al, 2021 ).…”

Section: Inhibitors and Activatorsmentioning

confidence: 99%

Epac: A Promising Therapeutic Target for Vascular Diseases: A Review

et al. 2022

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“…Hence, SOCS3 is an important crosstalk point between the Epac1/ Rap1 and the IL-6/JAK/STAT pathways. 32 In this study, we explored the role of Epac1-SOCS3 pathway and IL-6 signaling in CRF neurons on visceral hypersensitivity in rats that experienced neonatal CRD. Suppressor of cytokine signaling 3 is a canonical anti-inflammatory protein, with prominent immunoreactivity in the PVN and the rest of hypothalamus.…”

Section: Introductionmentioning

confidence: 99%

“…Activation of Epac can facilitate the accumulation of SOCS3, thereby resulting in the SOCS3‐dependent neuroinflammation suppression via inhibition of IL‐6 signaling. Hence, SOCS3 is an important crosstalk point between the Epac1/Rap1 and the IL‐6/JAK/STAT pathways 32 . In this study, we explored the role of Epac1‐SOCS3 pathway and IL‐6 signaling in CRF neurons on visceral hypersensitivity in rats that experienced neonatal CRD.…”

Section: Introductionmentioning

confidence: 99%