NF-κB and EGFR participate in S1PR3-mediated human renal cell carcinomas progression

Yan, Yali; Bao, Gegentuya; Pei, Jingyuan; Cao, Ying; Zhang, Chenyu; Zhao, Pengfei; Zhang, Yantao; Damirin, Alatangaole

doi:10.1016/j.bbadis.2022.166401

Cited by 10 publications

(4 citation statements)

References 33 publications

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“…S5 ) . Given that S1PR1 and S1PR2 are closely related to NF-κB 31 , 32 and the mitogen-activated protein kinases (MAPKs) pathway 33 , 34 , we further examined whether S1PR4 is associated with the activation of these pathways. S1pr4 -KO induced remarkable phosphorylation of c-Jun NH2-terminal kinase (JNK) instead of other pathways ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Sphingosine-1-Phosphate Receptor 4 Attenuates Neutrophilic Airway Inflammation in Experimental Asthma via Repressing Proinflammatory Macrophage Activation

Wang¹,

Tian²,

Lu³

et al. 2023

Int. J. Biol. Sci.

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Patients with eosinophilic asthma react well to conventional treatment of asthma while individualized therapy for non-eosinophilic endotypes have yet to be developed. Dysregulated sphingosine metabolites are associated with the pathophysiology of different asthma endotypes with their receptors involved. However, whether the sphingosine-1-phosphate receptor 4 (S1PR4) contributes to disease progression of asthma remains underappreciated. In this study, we demonstrated that sphingosine metabolism was disturbed in asthma while it could not be used to distinguish between different endotypes of asthma. S1PR4, a vital receptor of bioactive sphingosine metabolites and mainly expressed in macrophages, exhibited lower expression both in patients and experimental mice with neutrophilic airway inflammation. Additionally, S1pr4 deficiency aggravated the OVA/LPS-induced pulmonary inflammation in mice along with a significant up-regulation in M1 macrophage activation. Mechanistic studies showed that S1PR4 was strongly connected to bioactive oxylipins concurrent with bounding to formyl peptide receptor 2 to influence the phosphorylation of JNK and contributed to the macrophage M1 program, which in turn secreted amounts of inflammatory cytokines associated to the inflammatory response of neutrophilic asthma. Furthermore, treating mice with S1PR4 agonist CYM50308 was characterized by less pulmonary inflammatory infiltration. Our research indicates S1PR4 a promising therapeutic target for non-eosinophilic phenotypes of asthma.

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Section: Resultsmentioning

confidence: 99%

Sphingosine-1-Phosphate Receptor 4 Attenuates Neutrophilic Airway Inflammation in Experimental Asthma via Repressing Proinflammatory Macrophage Activation

Wang¹,

Tian²,

Lu³

et al. 2023

Int. J. Biol. Sci.

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“…Additionally, lower PD-L1 expression has been reported in metastatic uveal melanoma compared to metastatic cutaneous melanoma [ 2 ]. On the other hand, S1PR3 has been reported to be associated with tumorigenesis in lung cancer and renal cell carcinoma [ 20 , 23 ] but has not been reported in melanocytic tumors.…”

Section: Discussionmentioning

confidence: 99%

Missense mutation of NRAS is associated with malignant progression in neurocutaneous melanosis

Takahashi,

Natsumeda,

Hara

et al. 2024

acta neuropathol commun

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Neurocutaneous melanosis (NCM) is a rare congenital neurocutaneous syndrome characterized by congenital melanocytic nevus of skin and abnormal proliferation of leptomeningeal melanocytes. Early acquisition of post-zygotic somatic mutations has been postulated to underlie the pathogenesis of NCM. The pathogenesis of NCM remains to be fully elucidated, and treatment options have not been established. Here, we report for the first time, multiregional genomic analyses in a 3-year-old autopsied girl with leptomeningeal melanomatosis associated with NCM, in which a ventriculo-peritoneal (VP) shunt was inserted for the treatment of hydrocephalus. The patient expired six months after the onset due to respiratory failure caused by abdominal dissemination via VP shunt. We performed multiregional exome sequencing to identify genomic differences among brain and abdominal tumors, nevus, and normal tissues. A total of 87 somatic mutations were found in 71 genes, with a significantly large number of gene mutations found in the tumor site. The genetic alterations detected in the nevus were only few and not shared with other sites. Three mutations, namely GNAQ R183Q, S1PR3 G89S and NRAS G12V, considered pathogenic, were found, although S1PR3 mutations have not been previously reported in melanocytic tumors. GNAQ and S1PR3 mutations were shared in both tumor and normal sites. Moreover, the mutant allele frequencies of the two mutations were markedly higher in tumor sites than in normal sites, with copy-neutral loss-of-heterozygosity (CN-LOH) occurring in tumor. NRAS mutation was found only in the abdominal tumor and was thought to be responsible for malignant progression in the present case. Multiregional comprehensive genetic analysis may lead to discovering novel driver mutations associated with tumorigenesis and targeted therapy.

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“…Previous research has indicated an association between S1PR3 and the NF-κB pathway. Yan et al [ 46 ] reported that the NF-κB pathway participates in S1PR3-mediated human renal cell carcinoma progression, and Dong et al [ 47 ] reported that the S1PR3- NF‐κB axis may be a therapeutic target for ischaemic stroke. Moreover, previous studies have revealed the NF-κB-dependent proinflammatory role of the S1P/S1PR3 axis in lung adenocarcinoma cells, and the activation of S1PR3 facilitates tumour cell proliferation [ 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

S1PR3 inhibition protects against LPS-induced ARDS by inhibiting NF-κB and improving mitochondrial oxidative phosphorylation

Peng,

Tang,

et al. 2024

J Transl Med

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Background Inflammation and endothelial barrier dysfunction are the major pathophysiological changes in acute respiratory distress syndrome (ARDS). Sphingosine-1-phosphate receptor 3 (S1PR3), a G protein-coupled receptor, has been found to mediate inflammation and endothelial cell (EC) integrity. However, the function of S1PR3 in ARDS has not been fully elucidated. Methods We used a murine lipopolysaccharide (LPS)-induced ARDS model and an LPS- stimulated ECs model to investigate the role of S1PR3 in anti-inflammatory effects and endothelial barrier protection during ARDS. Results We found that S1PR3 expression was increased in the lung tissues of mice with LPS-induced ARDS. TY-52156, a selective S1PR3 inhibitor, effectively attenuated LPS-induced inflammation by suppressing the expression of proinflammatory cytokines and restored the endothelial barrier by repairing adherens junctions and reducing vascular leakage. S1PR3 inhibition was achieved by an adeno-associated virus in vivo and a small interfering RNA in vitro. Both the in vivo and in vitro studies demonstrated that pharmacological or genetic inhibition of S1PR3 protected against ARDS by inhibiting the NF-κB pathway and improving mitochondrial oxidative phosphorylation. Conclusions S1PR3 inhibition protects against LPS-induced ARDS via suppression of pulmonary inflammation and promotion of the endothelial barrier by inhibiting NF-κB and improving mitochondrial oxidative phosphorylation, indicating that S1PR3 is a potential therapeutic target for ARDS.

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NF-κB and EGFR participate in S1PR3-mediated human renal cell carcinomas progression

Cited by 10 publications

References 33 publications

Sphingosine-1-Phosphate Receptor 4 Attenuates Neutrophilic Airway Inflammation in Experimental Asthma via Repressing Proinflammatory Macrophage Activation

Sphingosine-1-Phosphate Receptor 4 Attenuates Neutrophilic Airway Inflammation in Experimental Asthma via Repressing Proinflammatory Macrophage Activation

Missense mutation of NRAS is associated with malignant progression in neurocutaneous melanosis

S1PR3 inhibition protects against LPS-induced ARDS by inhibiting NF-κB and improving mitochondrial oxidative phosphorylation

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