Abstract:
:Fibroblast growth factors (FGFs) play key roles in the pathogenesis of different human diseases, but the cross-talk between FGFs and other cytokines remains largely unexplored. We identified an unexpected antagonistic effect of FGFs on the interferon (IFN) signaling pathway. Genetic or pharmacological inhibition of FGF receptor signaling in keratinocytes promoted the expression of interferon-stimulated genes (ISG) and proteins in vitro and in vivo. Conversely, FGF7 or FGF10 treatment of keratinocytes suppressed ISG expression under homeostatic conditions and in response to IFN or poly(I:C) treatment. FGF-mediated ISG suppression was independent of IFN receptors, occurred at the transcriptional level, and required FGF receptor kinase and proteasomal activity. It is not restricted to keratinocytes and functionally relevant, since FGFs promoted the replication of herpes simplex virus I (HSV-1), lymphocytic choriomeningitis virus, and Zika virus. Most importantly, inhibition of FGFR signaling blocked HSV-1 replication in cultured human keratinocytes and in mice. These results suggest the use of FGFR kinase inhibitors for the treatment of viral infections.
journal_name
EMBO Mol Medjournal_title
EMBO molecular medicineauthors
Maddaluno L,Urwyler C,Rauschendorfer T,Meyer M,Stefanova D,Spörri R,Wietecha M,Ferrarese L,Stoycheva D,Bender D,Li N,Strittmatter G,Nasirujjaman K,Beer HD,Staeheli P,Hildt E,Oxenius A,Werner Sdoi
10.15252/emmm.201911793subject
Has Abstractpub_date
2020-09-07 00:00:00pages
e11793issue
9eissn
1757-4676issn
1757-4684journal_volume
12pub_type
杂志文章abstract::Metastatic castration-resistant prostate cancer (mCRPC) is a lethal form of treatment-resistant prostate cancer and poses significant therapeutic challenges. Deregulated receptor tyrosine kinase (RTK) signalling mediated by loss of tumour suppressor Sprouty2 (SPRY2) is associated with treatment resistance. Using pre-c...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201708347
更新日期:2018-04-01 00:00:00
abstract::A homozygous mutation in the gene for sigma 1 receptor (Sig1R) is a cause of inherited juvenile amyotrophic lateral sclerosis (ALS16). Sig1R localizes to the mitochondria-associated membrane (MAM), which is an interface of mitochondria and endoplasmic reticulum. However, the role of the MAM in ALS is not fully elucida...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201606403
更新日期:2016-12-01 00:00:00
abstract::Atherosclerosis, the major cause of cardiovascular disease, is a chronic inflammatory disease characterized by the accumulation of lipids and inflammatory cells in the artery wall. Aberrant expression of microRNAs has been implicated in the pathophysiological processes underlying the progression of atherosclerosis. He...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201607492
更新日期:2017-09-01 00:00:00
abstract::Breast cancer is a molecularly, biologically and clinically heterogeneous group of disorders. Understanding this diversity is essential to improving diagnosis and optimizing treatment. Both genetic and acquired epigenetic abnormalities participate in cancer, but the involvement of the epigenome in breast cancer and it...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201100801
更新日期:2011-12-01 00:00:00
abstract::The endocrine system is crucial for maintaining whole-body homeostasis. Little is known regarding endocrine hormones secreted by the heart other than atrial/brain natriuretic peptides discovered over 30 years ago. Here, we identify growth differentiation factor 15 (GDF15) as a heart-derived hormone that regulates body...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201707604
更新日期:2017-08-01 00:00:00
abstract::Mitochondrial (mt) diseases are multisystem disorders due to mutations in nuclear or mtDNA genes. Among the latter, more than 50% are located in transfer RNA (tRNA) genes and are responsible for a wide range of syndromes, for which no effective treatment is available at present. We show that three human mt aminoacyl-t...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201303198
更新日期:2014-02-01 00:00:00
abstract::Transferring large or multiple genes into primary human stem/progenitor cells is challenged by restrictions in vector capacity, and this hurdle limits the success of gene therapy. A paradigm is Duchenne muscular dystrophy (DMD), an incurable disorder caused by mutations in the largest human gene: dystrophin. The combi...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201607284
更新日期:2018-02-01 00:00:00
abstract::Angiogenic growth factors have recently been linked to tissue metabolism. We have used genetic gain- and loss-of function models to elucidate the effects and mechanisms of action of vascular endothelial growth factor-B (VEGF-B) in the heart. A cardiomyocyte-specific VEGF-B transgene induced an expanded coronary arteri...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201303147
更新日期:2014-03-01 00:00:00
abstract::The current seasonal inactivated influenza vaccine protects only against a narrow range of virus strains as it triggers a dominant antibody response toward the hypervariable hemagglutinin (HA) head region. The discovery of rare broadly protective antibodies against conserved regions in influenza virus proteins has pro...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201910938
更新日期:2020-05-08 00:00:00
abstract::On November 14 last year, the British Guardian published an account from an anonymous whistleblower at Google, accusing the company of misconduct in regard to handling sensitive health data. The whistleblower works for Project Nightingale, an attempt by Google to get into the lucrative US healthcare market, by storing...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.202012053
更新日期:2020-03-06 00:00:00
abstract::Nutrient availability is the major regulator of life and reproduction, and a complex cellular signaling network has evolved to adapt organisms to fasting. These sensor pathways monitor cellular energy metabolism, especially mitochondrial ATP production and NAD(+)/NADH ratio, as major signals for nutritional state. We ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201403943
更新日期:2014-06-01 00:00:00
abstract::Both the incidence and prevalence of inflammatory bowel disease (IBD) is increasing globally; in the industrialized world up to 0.5% of the population are affected and around 4.2 million individuals suffer from IBD in Europe and North America combined. Successful engraftment in experimental colitis models suggests tha...
journal_title:EMBO molecular medicine
pub_type: 杂志文章,评审
doi:10.15252/emmm.201607260
更新日期:2017-05-01 00:00:00
abstract::Diabetic nephropathy is the leading cause of end-stage renal disease. Although dysfunction of podocytes, also termed glomerular visceral epithelial cells, is critically associated with diabetic nephropathy, the mechanism underlying podocyte dysfunction still remains obscure. Here, we identify that KDM6A, a histone lys...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201809828
更新日期:2019-05-01 00:00:00
abstract::Mutations of the mitochondrial PTEN (phosphatase and tensin homologue)-induced kinase1 (PINK1) are important causes of recessive Parkinson disease (PD). Studies on loss of function and overexpression implicate PINK1 in apoptosis, abnormal mitochondrial morphology, impaired dopamine release and motor deficits. However,...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.200900006
更新日期:2009-05-01 00:00:00
abstract::Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessively inherited disorder with mental retardation (MR). Recently, mutations in the SIL1 gene, encoding a co-chaperone which regulates the chaperone HSPA5, were identified as a major cause of MSS. We here examined the pathophysiological significance of SIL1 muta...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201303069
更新日期:2014-03-01 00:00:00
abstract::Secreted Semaphorin 3E (Sema3E) promotes cancer cell invasiveness and metastatic spreading. The pro-metastatic activity of Sema3E is due to its proteolytic fragment p61, capable of transactivating the oncogenic tyrosine kinase ErbB2 that associates with the Sema3E receptor PlexinD1 in cancer cells. Here, we show that ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201100205
更新日期:2012-03-01 00:00:00
abstract::High T-cell infiltration in colorectal cancer (CRC) correlates with a favorable disease outcome and immunotherapy response. This, however, is only observed in a small subset of CRC patients. A better understanding of the factors influencing tumor T-cell responses in CRC could inspire novel therapeutic approaches to ac...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201910681
更新日期:2020-01-09 00:00:00
abstract::While increased VEGF-A has been associated with neovascular age-related macular degeneration (AMD), it is not known whether VEGF-A may also promote other age-related eye diseases. Here, we show that an increase in VEGF-A is sufficient to cause multiple distinct common aging diseases of the eye, including cataracts and...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201505613
更新日期:2016-03-01 00:00:00
abstract::The Plasmodium-infected hepatocyte has been considered necessary to prime the immune responses leading to sterile protection after vaccination with attenuated sporozoites. However, it has recently been demonstrated that priming also occurs in the skin. We wished to establish if sterile protection could be obtained in ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201201677
更新日期:2013-02-01 00:00:00
abstract::The insulin/insulin-like growth factor-1 signalling (IIS) pathway regulates cellular and organismal metabolism and controls the rate of aging. Gain-of-function mutations in p110α, the principal mammalian IIS-responsive isoform of PI 3-kinase (PI3K), promote cancer. In contrast, loss-of-function mutations in p110α impa...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201201953
更新日期:2013-04-01 00:00:00
abstract::Prevalence of type 2 diabetes (T2D) and obesity is increasing worldwide. Currently available therapies are not suited for all patients in the heterogeneous obese/T2D population, hence the need for novel treatments. Fibroblast growth factor 21 (FGF21) is considered a promising therapeutic agent for T2D/obesity. Native ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201708791
更新日期:2018-08-01 00:00:00
abstract::Dilated cardiomyopathy (DCM) is a life-threatening disorder whose genetic basis is heterogeneous and mostly unknown. Five Arab Christian infants, aged 4-30 months from four families, were diagnosed with DCM associated with mild skin, teeth, and hair abnormalities. All passed away before age 3. A homozygous sequence va...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201606523
更新日期:2017-03-01 00:00:00
abstract::Highly active antiretroviral therapy (HAART) has improved the outlook for the HIV epidemic, but does not provide a cure. The proposed "shock-and-kill" strategy is directed at inducing latent HIV reservoirs, which may then be purged via boosted immune response or targeting infected cells. We describe five novel compoun...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201708193
更新日期:2018-02-01 00:00:00
abstract::The current management of colorectal cancer (CRC) would greatly benefit from non-invasive prognostic biomarkers indicative of clinicopathological tumor characteristics. Here, we employed targeted proteomic profiling of 80 glycoprotein biomarker candidates across plasma samples of a well-annotated patient cohort with c...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201404874
更新日期:2015-09-01 00:00:00
abstract::Maladaptive plasticity involving increased expression of AMPA-type glutamate receptors is involved in several pathologies, including neuropathic pain, but direct inhibition of AMPARs is associated with side effects. As an alternative, we developed a cell-permeable, high-affinity (~2 nM) peptide inhibitor, Tat-P4 -(C5)...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201911248
更新日期:2020-06-08 00:00:00
abstract::The tumor suppressors Pten and p53 are frequently lost in breast cancer, yet the consequences of their combined inactivation are poorly understood. Here, we show that mammary-specific deletion of Pten via WAP-Cre, which targets alveolar progenitors, induced tumors with shortened latency compared to those induced by MM...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201404402
更新日期:2014-12-01 00:00:00
abstract::The nucleoside adenosine is a potent regulator of vascular homeostasis, but it remains unclear how expression or function of the adenosine-metabolizing enzyme adenosine kinase (ADK) and the intracellular adenosine levels influence angiogenesis. We show here that hypoxia lowered the expression of ADK and increased the ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201607066
更新日期:2017-09-01 00:00:00
abstract::Candida albicans is a frequent aetiologic agent of sepsis associated with high mortality in immunocompromised patients. Developing new antifungal therapies is a medical need due to the low efficiency and resistance to current antifungal drugs. Here, we show that p38γ and p38δ regulate the innate immune response to C. ...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201708485
更新日期:2018-05-01 00:00:00
abstract::Various disorders including pseudoxanthoma elasticum (PXE) and generalized arterial calcification of infancy (GACI), which are caused by inactivating mutations in ABCC6 and ENPP1, respectively, present with extensive tissue calcification due to reduced plasma pyrophosphate (PPi). However, it has always been assumed th...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.15252/emmm.201707532
更新日期:2017-11-01 00:00:00
abstract::Brain metastasis of breast cancer profoundly affects the cognitive and sensory functions as well as morbidity of patients, and the 1 year survival rate among these patients remains less than 20%. However, the pathological mechanism of brain metastasis is as yet poorly understood. In this report, we found that metastat...
journal_title:EMBO molecular medicine
pub_type: 杂志文章
doi:10.1002/emmm.201201623
更新日期:2013-03-01 00:00:00