Endothelin-1 could be one of the targets of psoriasis therapy

Simeone, Paola; Teson, Massimo; Latini, Alessandra; Carducci, M.; Venuti, Aldo

doi:10.1111/j.1365-2133.2004.06277.x

Cited by 14 publications

(12 citation statements)

References 9 publications

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“…Some of the keratinocytes can stimulate cell proliferation through an autocrine loop stimulated by peptides such as ET-1 (Simeone et al 2004). Control of this upregulated growth is an attractive mechanism for therapeutics (Simeone et al 2004). Modulation of ET-1 may be the target of such therapy of psoriasis (Simeone et al 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Endothelin-1 (ET-1) is produced in psoriatic keratinocytes and acts as an autocrine growth factor for these cells (Simeone et al 2004). MicroRNAs (miRNAs) are small noncoding RNAs of 19-24 nucleotides in length that function as posttranscriptional modulators of mRNA expression by suppressing mRNA translation or enhancing mRNA degradation (Amr et al 2016).…”

Section: Introductionmentioning

confidence: 99%

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Roles of miR-31 and Endothelin-1 in Psoriasis Vulgaris: Pathophysiological Functions and Potential Biomarkers

Borská¹,

Andrýs²,

Chmelařová³

et al. 2017

Physiol Res

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Psoriatic lesions are characterized by hyperproliferation, aberrant differentiation of keratinocytes resistant to apoptosis and inflammation. miR-31 plays pro-proliferative, pro-differentiative and pro-inflammatory roles and modulates apoptosis in psoriatic keratinocytes. Endothelin-1 (ET-1) is produced by psoriatic keratinocytes and suppresses apoptosis. Inflammation increases the production of ET-1, which in turn leads to the chronic stimulation of keratinocyte proliferation. The aim of this study was to identify the putative link between two potential biomarkers (miR-31 and ET-1) in patients with psoriasis. The study design included experimental group (29 patients with psoriasis), and the control group (22 blood donors). The PASI score evaluated the state of the disease (median: 18.6; interquartile range 14.5-20.9). Both, the serum level of ET-1 and the whole blood level of miR-31 were significantly increased (p<0.001 and p<0.05, respectively) in patients compared to the controls. However, a significant negative relationship between ET-1 and miR-31 was observed (Spearman’s rho=-037, p=0.05). It is possible that a negative feedback loop will be present between miR-31 and ET-1. Our results indicate that miR-31 and ET-1, potential biomarkers of the disease, play significant roles in the pathophysiology of psoriasis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Roles of miR-31 and Endothelin-1 in Psoriasis Vulgaris: Pathophysiological Functions and Potential Biomarkers

Borská¹,

Andrýs²,

Chmelařová³

et al. 2017

Physiol Res

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“…In growth factor-starved keratinocytes 16E5 enhances the mitogenic activity of endothelin-1 (ET-1) the specific ligand of ET A (Figure 2 ). Interestingly it was reported that the mitogenic activity of ET-1 may lead to the chronic stimulation of keratinocyte proliferation observed in psoriasis, an inflammatory/proliferative disorder of the skin, suggesting an important role for ET-1 in epithelial proliferation [ 78 ]. Furthermore cross-talking between ET A R and EGF-R pathways would have an amplifying effect on cell proliferation [ 79 ].…”

Section: Hpv E5mentioning

confidence: 99%

Papillomavirus E5: the smallest oncoprotein with many functions

Venuti¹,

Paolini²,

et al. 2011

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Papillomaviruses (PVs) are established agents of human and animal cancers. They infect cutaneous and mucous epithelia. High Risk (HR) Human PVs (HPVs) are consistently associated with cancer of the uterine cervix, but are also involved in the etiopathogenesis of other cancer types. The early oncoproteins of PVs: E5, E6 and E7 are known to contribute to tumour progression. While the oncogenic activities of E6 and E7 are well characterised, the role of E5 is still rather nebulous. The widespread causal association of PVs with cancer makes their study worthwhile not only in humans but also in animal model systems. The Bovine PV (BPV) system has been the most useful animal model in understanding the oncogenic potential of PVs due to the pivotal role of its E5 oncoprotein in cell transformation. This review will highlight the differences between HPV-16 E5 (16E5) and E5 from other PVs, primarily from BPV. It will discuss the targeting of E5 as a possible therapeutic agent.

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“…They are 21-residue peptides with 2 intramolecular disulphide bridges. Prominently known for with human psoriasis lesions [67][68][69] [70]) of series designed on a 3,3-diphenyl-2-(pyrimidin-2-yloxy)-propionic acid scaffold [61]. This series has antiinflammatory properties in models of ET-1 induced inflammation and cardiomyopathy and pancreatitis [71,72].…”

Section: Endothelin Receptorsmentioning

confidence: 97%

Nonpeptide Ligands That Target Peptide-Activated GPCRs In Inflammation

Blakeney¹,

Fairlie

2005

CMC

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The focus of this review is on G protein-coupled receptors (GPCRs) for which nonpeptidic ligands are known and have been evaluated for the treatment of inflammatory conditions. GPCRs are the most prevalent class of cell surface proteins in pharmaceutical research today, and GPCR-targeting drugs account for one tenth of worldwide pharmaceutical sales. Of over 800 human GPCRs identified to date, several hundred are activated by peptides/proteins and just over 30 of these have been identified so far as potential therapeutic targets for the treatment of inflammatory diseases. This review highlights those GPCRs and over 60 structurally diverse nonpeptidic compounds that interact with them and display pro- or anti- inflammatory properties. Among these GPCR targets are the receptors for peptides like bradykinin, chemokines, complement anaphylatoxins, corticotropin releasing factor, endothelins, melanocortins, tachykinins, urocortins, as well as the protease activated receptors (PARs). Other peptide activated GPCRs implicated in inflammation, like those that bind angiotensin II, N-formyl peptides, galanin, neuropeptide Y, opioids and oxytocin, are only briefly discussed because there is either less direct association with inflammation or few/no nonpeptidic antiinflammatory ligands known. While it is still very early in the development of antiinflammatory drugs that target GPCRs, there is already a wealth of information supporting their important roles as cellular sentries in inflammatory diseases. New opportunities are emerging to evaluate antiinflammatory activities of potent and selective GPCR-binding ligands, including those being developed for other disease indications. In summary, GPCRs deserve a great deal more attention as potential therapeutic targets in inflammatory diseases.

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Endothelin-1 could be one of the targets of psoriasis therapy

Cited by 14 publications

References 9 publications

Roles of miR-31 and Endothelin-1 in Psoriasis Vulgaris: Pathophysiological Functions and Potential Biomarkers

Roles of miR-31 and Endothelin-1 in Psoriasis Vulgaris: Pathophysiological Functions and Potential Biomarkers

Papillomavirus E5: the smallest oncoprotein with many functions

Nonpeptide Ligands That Target Peptide-Activated GPCRs In Inflammation

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