A transcriptional network underlies susceptibility to kidney disease progression.

Abstract:

:The molecular networks that control the progression of chronic kidney diseases (CKD) are poorly defined. We have recently shown that the susceptibility to development of renal lesions after nephron reduction is controlled by a locus on mouse chromosome 6 and requires epidermal growth factor receptor (EGFR) activation. Here, we identified microphthalmia-associated transcription factor A (MITF-A), a bHLH-Zip transcription factor, as a modifier of CKD progression. Sequence analysis revealed a strain-specific mutation in the 5' UTR that decreases MITF-A protein synthesis in lesion-prone friend virus B NIH (FVB/N) mice. More importantly, we dissected the molecular pathway by which MITF-A modulates CKD progression. MITF-A interacts with histone deacetylases to repress the transcription of TGF-α, a ligand of EGFR, and antagonizes transactivation by its related partner, transcription factor E3 (TFE3). Consistent with the key role of this network in CKD, Tgfa gene inactivation protected FVB/N mice from renal deterioration after nephron reduction. These data are relevant to human CKD, as we found that the TFE3/MITF-A ratio was increased in patients with damaged kidneys. Our study uncovers a novel transcriptional network and unveils novel potential prognostic and therapeutic targets for preventing human CKD progression.

journal_name

EMBO Mol Med

journal_title

EMBO molecular medicine

authors

Laouari D,Burtin M,Phelep A,Bienaime F,Noel LH,Lee DC,Legendre C,Friedlander G,Pontoglio M,Terzi F

doi

10.1002/emmm.201101127

subject

Has Abstract

pub_date

2012-08-01 00:00:00

pages

825-39

issue

8

eissn

1757-4676

issn

1757-4684

journal_volume

4

pub_type

杂志文章
  • Myeloid cell deficiency of p38γ/p38δ protects against candidiasis and regulates antifungal immunity.

    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

    authors: Alsina-Beauchamp D,Escós A,Fajardo P,González-Romero D,Díaz-Mora E,Risco A,Martín-Serrano MA,Del Fresno C,Dominguez-Andrés J,Aparicio N,Zur R,Shpiro N,Brown GD,Ardavín C,Netea MG,Alemany S,Sanz-Ezquerro JJ,Cuenda A

    更新日期:2018-05-01 00:00:00

  • Salvaging hope: Is increasing NAD(+) a key to treating mitochondrial myopathy?

    abstract::Mitochondrial diseases can arise from mutations either in mitochondrial DNA or in nuclear DNA encoding mitochondrially destined proteins. Currently, there is no cure for these diseases although treatments to ameliorate a subset of the symptoms are being developed. In this issue of EMBO Molecular Medicine, Khan et al (...

    journal_title:EMBO molecular medicine

    pub_type: 评论,杂志文章

    doi:10.15252/emmm.201404179

    authors: Lightowlers RN,Chrzanowska-Lightowlers ZM

    更新日期:2014-06-01 00:00:00

  • VEGF-C is required for intestinal lymphatic vessel maintenance and lipid absorption.

    abstract::Vascular endothelial growth factor C (VEGF-C) binding to its tyrosine kinase receptor VEGFR-3 drives lymphatic vessel growth during development and in pathological processes. Although the VEGF-C/VEGFR-3 pathway provides a target for treatment of cancer and lymphedema, the physiological functions of VEGF-C in adult vas...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201505731

    authors: Nurmi H,Saharinen P,Zarkada G,Zheng W,Robciuc MR,Alitalo K

    更新日期:2015-11-01 00:00:00

  • Modification of γ-secretase by nitrosative stress links neuronal ageing to sporadic Alzheimer's disease.

    abstract::Inherited familial Alzheimer's disease (AD) is characterized by small increases in the ratio of Aβ42 versus Aβ40 peptide which is thought to drive the amyloid plaque formation in the brain of these patients. Little is known however whether ageing, the major risk factor for sporadic AD, affects amyloid beta-peptide (Aβ...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201200243

    authors: Guix FX,Wahle T,Vennekens K,Snellinx A,Chávez-Gutiérrez L,Ill-Raga G,Ramos-Fernandez E,Guardia-Laguarta C,Lleó A,Arimon M,Berezovska O,Muñoz FJ,Dotti CG,De Strooper B

    更新日期:2012-07-01 00:00:00

  • Compounds producing an effective combinatorial regimen for disruption of HIV-1 latency.

    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

    authors: Hashemi P,Barreto K,Bernhard W,Lomness A,Honson N,Pfeifer TA,Harrigan PR,Sadowski I

    更新日期:2018-02-01 00:00:00

  • Oligonucleotide-induced alternative splicing of serotonin 2C receptor reduces food intake.

    abstract::The serotonin 2C receptor regulates food uptake, and its activity is regulated by alternative pre-mRNA splicing. Alternative exon skipping is predicted to generate a truncated receptor protein isoform, whose existence was confirmed with a new antiserum. The truncated receptor sequesters the full-length receptor in int...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201506030

    authors: Zhang Z,Shen M,Gresch PJ,Ghamari-Langroudi M,Rabchevsky AG,Emeson RB,Stamm S

    更新日期:2016-08-01 00:00:00

  • An essential role for decorin in bladder cancer invasiveness.

    abstract::Muscle-invasive forms of urothelial carcinomas are responsible for most mortality in bladder cancer. Finding new treatments for invasive bladder tumours requires adequate animal models to decipher the mechanisms of progression, in particular the way tumours interact with their microenvironment. Herein, using the murin...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201302655

    authors: El Behi M,Krumeich S,Lodillinsky C,Kamoun A,Tibaldi L,Sugano G,De Reynies A,Chapeaublanc E,Laplanche A,Lebret T,Allory Y,Radvanyi F,Lantz O,Eiján AM,Bernard-Pierrot I,Théry C

    更新日期:2013-12-01 00:00:00

  • Spotlight on Mycobacteria and dendritic cells: will novel targets to fight tuberculosis emerge?

    abstract::Over thousands of years microbes and mammals have co-evolved, resulting in extraordinarily sophisticated molecular mechanisms permitting the organisms to survive together. Mycobacterium tuberculosis is one of the best examples of successful co-evolution, since the bacilli have infected one third of the human populatio...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章,评审

    doi:10.1002/emmm.200900008

    authors: Mortellaro A,Robinson L,Ricciardi-Castagnoli P

    更新日期:2009-04-01 00:00:00

  • Metronomic chemotherapy offsets HIFα induction upon maximum-tolerated dose in metastatic cancers.

    abstract::Conventional maximum-tolerated dose (MTD) chemotherapy relies on periodic, massive cancer cell ablation events followed by treatment-free intermissions, stereotypically resulting in resistance, relapse, and mortality. Furthermore, MTD chemotherapy can promote metastatic dissemination via activation of a transcriptiona...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201911416

    authors: Schito L,Rey S,Xu P,Man S,Cruz-Muñoz W,Kerbel RS

    更新日期:2020-09-07 00:00:00

  • iPhemap: an atlas of phenotype to genotype relationships of human iPSC models of neurological diseases.

    abstract::Disease modeling with induced pluripotent stem cells (iPSCs) is creating an abundance of phenotypic information that has become difficult to follow and interpret. Here, we report a systematic analysis of research practices and reporting bias in neurological disease models from 93 published articles. We find heterogene...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201708191

    authors: Hollingsworth EW,Vaughn JE,Orack JC,Skinner C,Khouri J,Lizarraga SB,Hester ME,Watanabe F,Kosik KS,Imitola J

    更新日期:2017-12-01 00:00:00

  • Long-term p110α PI3K inactivation exerts a beneficial effect on metabolism.

    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

    authors: Foukas LC,Bilanges B,Bettedi L,Pearce W,Ali K,Sancho S,Withers DJ,Vanhaesebroeck B

    更新日期:2013-04-01 00:00:00

  • Hypoxic priming of mESCs accelerates vascular-lineage differentiation through HIF1-mediated inverse regulation of Oct4 and VEGF.

    abstract::Hypoxic microenvironment plays an important role in determining stem cell fates. However, it is controversial to which direction between self-renewal and differentiation the hypoxia drives the stem cells. Here, we investigated whether a short exposure to hypoxia (termed 'hypoxic-priming') efficiently directed and prom...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201101107

    authors: Lee SW,Jeong HK,Lee JY,Yang J,Lee EJ,Kim SY,Youn SW,Lee J,Kim WJ,Kim KW,Lim JM,Park JW,Park YB,Kim HS

    更新日期:2012-09-01 00:00:00

  • Sequence variation in PPP1R13L results in a novel form of cardio-cutaneous syndrome.

    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

    authors: Falik-Zaccai TC,Barsheshet Y,Mandel H,Segev M,Lorber A,Gelberg S,Kalfon L,Ben Haroush S,Shalata A,Gelernter-Yaniv L,Chaim S,Raviv Shay D,Khayat M,Werbner M,Levi I,Shoval Y,Tal G,Shalev S,Reuveni E,Avitan-Hersh E,V

    更新日期:2017-03-01 00:00:00

  • Reactive astrocytes promote the metastatic growth of breast cancer stem-like cells by activating Notch signalling in brain.

    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

    authors: Xing F,Kobayashi A,Okuda H,Watabe M,Pai SK,Pandey PR,Hirota S,Wilber A,Mo YY,Moore BE,Liu W,Fukuda K,Iiizumi M,Sharma S,Liu Y,Wu K,Peralta E,Watabe K

    更新日期:2013-03-01 00:00:00

  • A novel small molecule RAD51 inactivator overcomes imatinib-resistance in chronic myeloid leukaemia.

    abstract::RAD51 recombinase activity plays a critical role for cancer cell proliferation and survival, and often contributes to drug-resistance. Abnormally elevated RAD51 function and hyperactive homologous recombination (HR) rates have been found in a panel of cancers, including breast cancer and chronic myeloid leukaemia (CML...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201201760

    authors: Zhu J,Zhou L,Wu G,Konig H,Lin X,Li G,Qiu XL,Chen CF,Hu CM,Goldblatt E,Bhatia R,Chamberlin AR,Chen PL,Lee WH

    更新日期:2013-03-01 00:00:00

  • Genomic data sharing in Europe is stumbling-Could a code of conduct prevent its fall?

    abstract::Genomic data sharing is becoming more important as scientists join forces across borders in biomedical research for the benefit of patients and society. The EU's General Data Protection Regulation (GDPR) helps simplify sharing of such data at the European and international level. However, initial optimism has dried up...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201911421

    authors: Molnár-Gábor F,Korbel JO

    更新日期:2020-03-06 00:00:00

  • Dietary magnesium supplementation improves lifespan in a mouse model of progeria.

    abstract::Aging is associated with redox imbalance according to the redox theory of aging. Consistently, a mouse model of premature aging (LmnaG609G/+ ) showed an increased level of mitochondrial reactive oxygen species (ROS) and a reduced basal antioxidant capacity, including loss of the NADPH-coupled glutathione redox system....

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.202012423

    authors: Villa-Bellosta R

    更新日期:2020-10-07 00:00:00

  • Google's Project Nightingale highlights the necessity of data science ethics review.

    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

    authors: Schneble CO,Elger BS,Shaw DM

    更新日期:2020-03-06 00:00:00

  • Prolyl-isomerase Pin1 controls normal and cancer stem cells of the breast.

    abstract::Mammary epithelial stem cells are fundamental to maintain tissue integrity. Cancer stem cells (CSCs) are implicated in both treatment resistance and disease relapse, and the molecular bases of their malignant properties are still poorly understood. Here we show that both normal stem cells and CSCs of the breast are co...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201302909

    authors: Rustighi A,Zannini A,Tiberi L,Sommaggio R,Piazza S,Sorrentino G,Nuzzo S,Tuscano A,Eterno V,Benvenuti F,Santarpia L,Aifantis I,Rosato A,Bicciato S,Zambelli A,Del Sal G

    更新日期:2014-01-01 00:00:00

  • Zinc inhibits lethal inflammatory shock by preventing microbe-induced interferon signature in intestinal epithelium.

    abstract::The cytokine TNF drives inflammatory diseases, e.g., Crohn's disease. In a mouse model of TNF-induced systemic inflammatory response syndrome (SIRS), severe impact on intestinal epithelial cells (IECs) is observed. Zinc confers complete protection in this model. We found that zinc no longer protects in animals which l...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201911917

    authors: Souffriau J,Timmermans S,Vanderhaeghen T,Wallaeys C,Van Looveren K,Aelbrecht L,Dewaele S,Vandewalle J,Goossens E,Verbanck S,Boyen F,Eggermont M,De Commer L,De Rycke R,De Bruyne M,Tito R,Ballegeer M,Vandevyver S,Velho

    更新日期:2020-10-07 00:00:00

  • FGF21 gene therapy as treatment for obesity and insulin resistance.

    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

    authors: Jimenez V,Jambrina C,Casana E,Sacristan V,Muñoz S,Darriba S,Rodó J,Mallol C,Garcia M,León X,Marcó S,Ribera A,Elias I,Casellas A,Grass I,Elias G,Ferré T,Motas S,Franckhauser S,Mulero F,Navarro M,Haurigot V,Rube

    更新日期:2018-08-01 00:00:00

  • Making the most of what you've got: optimizing residual OXPHOS function in mitochondrial diseases.

    abstract::Patients affected by mitochondrial OXPHOS disorders are still faced with a grim lack of therapeutic options. In this Closeup, Carlos Moraes revisits the recent data by Giovanni Manfredi on PKA's functions in the mitochondria and now its modulation can improve respiration and ATP production in COX-defective cells. ...

    journal_title:EMBO molecular medicine

    pub_type: 评论,杂志文章

    doi:10.1002/emmm.200900049

    authors: Moraes CT

    更新日期:2009-11-01 00:00:00

  • Early 5-HT6 receptor blockade prevents symptom onset in a model of adolescent cannabis abuse.

    abstract::Cannabis abuse during adolescence confers an increased risk for developing later in life cognitive deficits reminiscent of those observed in schizophrenia, suggesting common pathological mechanisms that remain poorly characterized. In line with previous findings that revealed a role of 5-HT6 receptor-operated mTOR act...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201910605

    authors: Berthoux C,Hamieh AM,Rogliardo A,Doucet EL,Coudert C,Ango F,Grychowska K,Chaumont-Dubel S,Zajdel P,Maldonado R,Bockaert J,Marin P,Bécamel C

    更新日期:2020-05-08 00:00:00

  • GDF15 is a heart-derived hormone that regulates body growth.

    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

    authors: Wang T,Liu J,McDonald C,Lupino K,Zhai X,Wilkins BJ,Hakonarson H,Pei L

    更新日期:2017-08-01 00:00:00

  • Disease-specific phenotypes in iPSC-derived neural stem cells with POLG mutations.

    abstract::Mutations in POLG disrupt mtDNA replication and cause devastating diseases often with neurological phenotypes. Defining disease mechanisms has been hampered by limited access to human tissues, particularly neurons. Using patient cells carrying POLG mutations, we generated iPSCs and then neural stem cells. These neural...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.202012146

    authors: Liang KX,Kristiansen CK,Mostafavi S,Vatne GH,Zantingh GA,Kianian A,Tzoulis C,Høyland LE,Ziegler M,Perez RM,Furriol J,Zhang Z,Balafkan N,Hong Y,Siller R,Sullivan GJ,Bindoff LA

    更新日期:2020-10-07 00:00:00

  • Defective glutamate and K+ clearance by cortical astrocytes in familial hemiplegic migraine type 2.

    abstract::Migraine is a common disabling brain disorder. A subtype of migraine with aura (familial hemiplegic migraine type 2: FHM2) is caused by loss-of-function mutations in α2 Na(+),K(+) ATPase (α2 NKA), an isoform almost exclusively expressed in astrocytes in adult brain. Cortical spreading depression (CSD), the phenomenon ...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.15252/emmm.201505944

    authors: Capuani C,Melone M,Tottene A,Bragina L,Crivellaro G,Santello M,Casari G,Conti F,Pietrobon D

    更新日期:2016-08-01 00:00:00

  • TSC22D4 is a molecular output of hepatic wasting metabolism.

    abstract::In mammals, proper storage and distribution of lipids in and between tissues is essential for the maintenance of energy homeostasis. Here, we show that tumour growth triggers hepatic metabolic dysfunction as part of the cancer cachectic phenotype, particularly by reduced hepatic very-low-density-lipoprotein (VLDL) sec...

    journal_title:EMBO molecular medicine

    pub_type: 杂志文章

    doi:10.1002/emmm.201201869

    authors: Jones A,Friedrich K,Rohm M,Schäfer M,Algire C,Kulozik P,Seibert O,Müller-Decker K,Sijmonsma T,Strzoda D,Sticht C,Gretz N,Dallinga-Thie GM,Leuchs B,Kögl M,Stremmel W,Diaz MB,Herzig S

    更新日期:2013-02-01 00:00:00

  • Combined deletion of Pten and p53 in mammary epithelium accelerates triple-negative breast cancer with dependency on eEF2K.

    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

    authors: Liu JC,Voisin V,Wang S,Wang DY,Jones RA,Datti A,Uehling D,Al-awar R,Egan SE,Bader GD,Tsao M,Mak TW,Zacksenhaus E

    更新日期:2014-12-01 00:00:00

  • A KDM6A-KLF10 reinforcing feedback mechanism aggravates diabetic podocyte dysfunction.

    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

    authors: Lin CL,Hsu YC,Huang YT,Shih YH,Wang CJ,Chiang WC,Chang PJ

    更新日期:2019-05-01 00:00:00

  • Targeting cardiac hypertrophy through a nuclear co-repressor.

    abstract::Heart failure entails the inability of the heart to pump blood to vital organs. One of the main risk factors for heart failure is the development of pathological hypertrophy. In this issue of EMBO Molecular Medicine, Li and coworkers show that NCoR1, a co-repressor of transcription factors, inhibits the transcriptiona...

    journal_title:EMBO molecular medicine

    pub_type: 评论,杂志文章

    doi:10.15252/emmm.201911297

    authors: Grund A,Heineke J

    更新日期:2019-11-07 00:00:00