Sphingosine 1-phosphate stimulates eyelid closure in the developing rat by stimulating EGFR signaling

In many mammals, the eyelids migrate over the eye and fuse during embryogenesis to protect the cornea from damage during birth and early life. Loss-of-function mutations affecting the epidermal growth factor receptor (EGFR) signaling pathway cause an eyes-open-at-birth (EOB) phenotype in rodents. We identified an insertional mutation in Spinster homolog 2 (Spns2) in a strain of transgenic rats exhibiting the EOB phenotype. Spns2, a sphingosine 1-phosphate (S1P) transporter that releases S1P from cells, was enriched at the tip of developing eyelids in wild-type rat embryos. Spns2 expression or treatment with S1P or any one of several EGFR ligands rescued the EOB Spns2 mutant phenotype in vivo and in tissue explants in vitro and rescued the formation of stress fibers in primary keratinocytes from mutants. S1P signaled through the receptors S1PR1, S1PR2, and S1PR3 to activate extracellular signal–regulated kinase (ERK) and EGFR-dependent mitogen-activated protein kinase kinase kinase 1 (MEKK1)–c-Jun signaling. S1P also induced the nuclear translocation of the transcription factor MAL in a manner dependent on EGFR signaling. MAL and c-Jun stimulated the expression of the microRNAs miR-21 and miR-222, both of which target the metalloprotease inhibitor TIMP3, thus promoting metalloprotease activity. The metalloproteases ADAM10 and ADAM17 stimulated EGFR signaling by cleaving a membrane-anchored form of EGF to release the ligand. Our results outline a network by which S1...
Source: Signal Transduction Knowledge Environment - Category: Science Authors: Tags: STKE Research Articles Source Type: news

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Conclusions: A phenotype corresponding to combined monosomy 6p25 and trisomy 18p11 presented as childhood glaucoma associated with non-acquired (congenital) ocular anomalies consist of aniridia and Peters anomaly and other systemic malformations. To the best of our knowledge, this is the first report which demonstrated the breakpoint sequence of an unbalanced translocation in a Japanese infant with childhood glaucoma. PMID: 32223580 [PubMed - as supplied by publisher]
Source: Ophthalmic Genetics - Category: Opthalmology Tags: Ophthalmic Genet Source Type: research
Exposure to low ozone concentrations is used in medicine as an adjuvant/complementary treatment for a variety of diseases. The therapeutic potential of low ozone concentrations relies on their capability to increase the nuclear translocation of the Nuclear factor erythroid 2-related factor 2 (Nrf2), thus inducing the transcription of Antioxidant Response Elements (ARE)-driven genes and, through a cascade of events, a general cytoprotective response. However, based on the controversial role of Nrf2 in cancer initiation, progression and resistance to therapies, possible negative effects of ozone therapy may be hypothesised i...
Source: European Journal of Histochemistry - Category: Biomedical Science Source Type: research
This study presents a primarily qualitative analysis of contacts of non-homologous chromosomes by short arms, during meiotic prophase I in the mole vole, Ellobius alaicus, a species with a variable karyotype, due to Robertsonian translocations. Immunocytochemical staining of spermatocytes demonstrated the presence of four contact types for non-homologous chromosomes in meiotic prophase I: (1) proximity, (2) touching, (3) anchoring/tethering, and (4) fusion. Our results suggest distinct mechanisms for chromosomal interactions in meiosis. Thus, we propose to change the translocation mechanism model from ‘contact fi...
Source: Genes - Category: Genetics & Stem Cells Authors: Tags: Article Source Type: research
Publication date: 31 March 2020Source: Cell Reports, Volume 30, Issue 13Author(s): Sneha Shah, Gemma Molinaro, Botao Liu, Ruijia Wang, Kimberly M. Huber, Joel D. Richter
Source: Cell Reports - Category: Cytology Source Type: research
Coordinated assembly and disassembly of integrin-mediated focal adhesions (FAs) is essential for cell migration. Many studies have shown that FA disassembly requires Ca2+ influx, however our understanding of this process remains incomplete. Here we show that Ca2+ influx via STIM1/Orai1 calcium channels, which cluster near FAs, leads to activation of the GTPase Arf5 via the Ca2+-activated GEF IQSec1, and that both IQSec1 and Arf5 activation are essential for adhesion disassembly. We further show that IQSec1 forms a complex with the lipid transfer protein ORP3, and that Ca2+ influx triggers PKC-dependent translocation of thi...
Source: eLife - Category: Biomedical Science Tags: Cell Biology Source Type: research
In conclusion, nicardipine exerted anti-inflammatory effects through inhibiting NLRP3 inflammasome pathway. Nicardipine may mitigate NLRP3 primingvia inhibiting NF-kappaB activation, mediated by suppressing LPS-induced TLR4 expression.
Source: Inflammation - Category: Allergy & Immunology Source Type: research
In conclusion, the protective effect of HDL to counter ER stress and β-cell death involves the transport, generation, and mobilization of oxysterols for activation of the Hh signaling receptor SMO
Source: The Journal of Lipid Research - Category: Lipidology Authors: Tags: Research Articles Source Type: research
ndar Xiuqing Wang A greenhouse pot trial was conducted to investigate the effect of organic amendments combined with triple superphosphate on the bioavailability of heavy metals (HMs), Amorpha fruticosa growth and metal uptake from Pb-Zn mine tailings. Cattle manure compost (CMC), spent mushroom compost (SMC) and agricultural field soil (AFS) were applied to tailings at 5%, 10%, 20% and 30% w/w ratio, whereas sewage sludge (SS) and wood biochar (WB) were mixed at 2.5%, 5%, 10% and 20% w/w ratio. Triple superphosphate (TSP) was added to all the treatments at 4:1 (molar ratio). Amendments efficiently decreased DTPA-ext...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
Authors: Jia M, Xiong Y, Li M, Mao Q Abstract Chemotherapy is critical for the treatment of hepatocellular carcinoma (HCC). Despite the pro-apoptotic effects of corosolic acid (CA) treatment, its underlying mechanism is not completely clear. The aim of this study was to determine the molecular mechanism of CA in HCC treatment. MTT assay was used to determine the IC50 of CA. Immunoprecipitation and immunofluorescence were used to detect the interaction between and subcellular localization of Yes-associated protein (YAP) and mouse double minute 2 (MDM2). In addition, in vivo xenotransplantation was performed to asses...
Source: Oncology Research - Category: Cancer & Oncology Tags: Oncol Res Source Type: research
In conclusion, sitagliptin may have a potential inhibitory effect on GC by AMPK/YAP/melanoma‐associated antigen‐A3 pathway.
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research
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