Cyclosporine A induces endothelin‐converting enzyme‐1: Studies in vivo and in vitro

Heyman, Samuel N.; Abassi, Zaid; Rosenberger, Christian; Yaseen, Hiba; Skarjinski, G.; Shina, Ahuva; Mathia, Susanne; Krits, N.; Khamaisi, Mogher

doi:10.1111/apha.13033

Cited by 10 publications

(6 citation statements)

References 59 publications

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“…The negative side effects of calcineurin inhibitors such as cyclosporine and tacrolimus are associated with the activation of both renin-angiotensin and endothelin systems (Hošková et al 2017). The mechanism underlying nephrotoxic effects of cyclosporine A (CSA) is connected with the induction of endothelin-converting enzyme by CSA resulting in ET-1 generation which leads to further renal hypoxia and ET-1 synthesis (Heyman et al 2018). Blockade of ET A receptors with atrasentan ameliorated nephrotoxic effects induced by a combination of CSA with indomethacin, including positive effects on renal function and inhibition of oxidative stress (Helmy et al 2015).…”

Section: Endothelin Antagonists In Experimental Non-diabetic Ckdmentioning

confidence: 99%

Renoprotective Effects of ETA Receptor Antagonists Therapy in Experimental Non-Diabetic Chronic Kidney Disease: Is There Still Hope for the Future?

Vaněčková

Hojná²,

Kadlecová³

et al. 2018

Physiol Res

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Chronic kidney disease (CKD) is a life-threatening disease arising as a frequent complication of diabetes, obesity and hypertension. Since it is typically undetected for long periods, it often progresses to end-stage renal disease. CKD is characterized by the development of progressive glomerulosclerosis, interstitial fibrosis and tubular atrophy along with a decreased glomerular filtration rate. This is associated with podocyte injury and a progressive rise in proteinuria. As endothelin-1 (ET-1) through the activation of endothelin receptor type A (ETA) promotes renal cell injury, inflammation, and fibrosis which finally lead to proteinuria, it is not surprising that ETA receptors antagonists have been proven to have beneficial renoprotective effects in both experimental and clinical studies in diabetic and non-diabetic CKD. Unfortunately, fluid retention encountered in large clinical trials in diabetic CKD led to the termination of these studies. Therefore, several advances, including the synthesis of new antagonists with enhanced pharmacological activity, the use of lower doses of ET antagonists, the addition of diuretics, plus simply searching for distinct pathological states to be treated, are promising targets for future experimental studies. In support of these approaches, our group demonstrated in adult subtotally nephrectomized Ren-2 transgenic rats that the addition of a diuretic on top of renin-angiotensin and ETA blockade led to a further decrease of proteinuria. This effect was independent of blood pressure which was normalized in all treated groups. Recent data in non-diabetic CKD, therefore, indicate a new potential for ETA antagonists, at least under certain pathological conditions.

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Section: Endothelin Antagonists In Experimental Non-diabetic Ckdmentioning

confidence: 99%

Renoprotective Effects of ETA Receptor Antagonists Therapy in Experimental Non-Diabetic Chronic Kidney Disease: Is There Still Hope for the Future?

Vaněčková

Hojná²,

Kadlecová³

et al. 2018

Physiol Res

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“…6 Although pathophysiology of CsA-induced kidney injury remains incompletely understood, hypoxia of nephron segments likely is involved. 7 Mice receiving CsA repetitively over days experience episodic kidney hypoxia. 8 Interestingly, some groups report anemia under CsA treatment, 9,10 as well as relatively low erythropoietin (EPO) blood levels.…”

mentioning

confidence: 99%

Daprodustat prevents cyclosporine-A–mediated anemia and peritubular capillary loss

Labes

Brinkmann

Kulow

et al. 2022

Kidney International

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“…Therefore, the identification of new molecular targets and molecular pathways is useful for providing new insights into the treatment and prognosis of LUAD. Previous research has demonstrated that all four subtypes of ECE2 are located in endocrine vesicles and capable of degrading intracellular neuropeptides under mildly acidic conditions ( 24 ). ECE2 is mainly expressed in neural tissues ( 8 ).…”

Section: Discussionmentioning

confidence: 99%

ECE2 is a prognostic biomarker associated with m6A modification and involved in immune infiltration of lung adenocarcinoma

et al. 2022

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BackgroundThe targeted therapy for lung cancer relies on prognostic genes and requires further research. No research has been conducted to determine the effect of endothelin-converting enzyme 2 (ECE2) in lung cancer.MethodsWe analyzed the expression of ECE2 in lung adenocarcinoma (LUAD) and normal adjacent tissues and its relationship with clinicopathological characteristics from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO). Immunohistochemical staining was used to further validate the findings. GO/KEGG enrichment analysis and gene set enrichment analysis (GSEA) of ECE2 co-expression were performed using R software. Data from TIMER, the GEPIA database, and TCGA were analyzed to determine the relationship between ECE2 expression and LUAD immune infiltration. To investigate the relationship between ECE2 expression levels and LUAD m6A modification, TCGA data and GEO data were analyzed.ResultsECE2 is highly expressed in various cancers including LUAD. ECE2 showed high accuracy in distinguishing tumor and normal sample results. The expression level of ECE2 in LUAD was significantly correlated with tumor stage and prognosis. GO/KEGG enrichment analysis showed that ECE2 was closely related to mitochondrial gene expression, ATPase activity and cell cycle. GSEA analysis showed that ECE2-related differential gene enrichment pathways were related to mitotic cell cycle, MYC pathway, PLK1 pathway, DNA methylation pathway, HIF1A pathway and Oxidative stress-induced cellular senescence. Analysis of the TIMER, GEPIA database, and TCGA datasets showed that ECE2 expression levels were significantly negatively correlated with B cells, CD4+ cells, M2 macrophages, neutrophils, and dendritic cells. TCGA and GEO datasets showed that ECE2 was significantly associated with m6A modification-related genes HNRNPC, IGF2BP1, IGF2BP3 and RBM1.ConclusionECE2 is associated with m6A modification and immune infiltration and is a prognostic biomarker in LUAD.

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Cyclosporine A induces endothelin‐converting enzyme‐1: Studies in vivo and in vitro

Abstract: CsA induces ECE-1 via both hypoxic and non-hypoxic pathways. ECE-1 may contribute to increased renal ET-1 generation following CsA, participating in a feed-forward loop of renal parenchymal hypoxia and ET synthesis.

Cited by 10 publications

References 59 publications

Renoprotective Effects of ETA Receptor Antagonists Therapy in Experimental Non-Diabetic Chronic Kidney Disease: Is There Still Hope for the Future?

Renoprotective Effects of ETA Receptor Antagonists Therapy in Experimental Non-Diabetic Chronic Kidney Disease: Is There Still Hope for the Future?

Daprodustat prevents cyclosporine-A–mediated anemia and peritubular capillary loss

ECE2 is a prognostic biomarker associated with m6A modification and involved in immune infiltration of lung adenocarcinoma

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