Abstract：
:The amount and distribution of dystrophin protein in myofibers and muscle is highly variable in Becker muscular dystrophy and in exon-skipping trials for Duchenne muscular dystrophy. Here, we investigate a molecular basis for this variability. In muscle from Becker patients sharing the same exon 45-47 in-frame deletion, dystrophin levels negatively correlate with microRNAs predicted to target dystrophin. Seven microRNAs inhibit dystrophin expression in vitro, and three are validated in vivo (miR-146b/miR-374a/miR-31). microRNAs are expressed in dystrophic myofibers and increase with age and disease severity. In exon-skipping-treated mdx mice, microRNAs are significantly higher in muscles with low dystrophin rescue. TNF-α increases microRNA levels in vitro whereas NFκB inhibition blocks this in vitro and in vivo. Collectively, these data show that microRNAs contribute to variable dystrophin levels in muscular dystrophy. Our findings suggest a model where chronic inflammation in distinct microenvironments induces pathological microRNAs, initiating a self-sustaining feedback loop that exacerbates disease progression.
journal_name
Cell Repjournal_title
Cell reportsauthors
Fiorillo AA,Heier CR,Novak JS,Tully CB,Brown KJ,Uaesoontrachoon K,Vila MC,Ngheim PP,Bello L,Kornegay JN,Angelini C,Partridge TA,Nagaraju K,Hoffman EPdoi
10.1016/j.celrep.2015.07.066subject
Has Abstractpub_date
2015-09-08 00:00:00pages
1678-90issue
10issn
2211-1247pii
S2211-1247(15)00856-6journal_volume
12pub_type
杂志文章相关文献
Cell Reports文献大全abstract：:Inhibition of the ATPase cycle of the HSP90 chaperone promotes ubiquitylation and proteasomal degradation of its client proteins, which include many oncogenic protein kinases. This provides the rationale for HSP90 inhibitors as cancer therapeutics. However, the mechanism by which HSP90 ATPase inhibition triggers ubiqu...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2017.05.078
更新日期：2017-06-20 00:00:00
abstract：:Inflammatory bowel disease (IBD) is prevalent, but the mechanisms underlying disease development remain elusive. We identify a role for the E3 ubiquitin ligase RNF5 in IBD. Intestinal epithelial cells (IECs) express a high level of RNF5, while the colon of Rnf5-/- mice exhibits activated dendritic cells and intrinsic ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.08.057
更新日期：2018-09-18 00:00:00
abstract：:Adrenergic receptors are highly homologous while at the same time display a wide diversity of ligand and G-protein binding, and understanding this diversity is key for designing selective or biased drugs for them. Here, we determine two crystal structures of the α2A adrenergic receptor (α2AAR) in complex with a partia...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.10.088
更新日期：2019-12-03 00:00:00
abstract：:Pancreatitis is an inflammatory disease of the exocrine pancreas and ranks among the most common gastrointestinal disorders. Inflamed tissues frequently experience conditions of insufficient oxygen availability, or hypoxia. Here, we demonstrate that hypoxia and consequent stabilization of the hypoxia-inducible factor ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.05.071
更新日期：2018-06-19 00:00:00
abstract：:Development and function of pancreatic β cells involve the regulated activity of specific transcription factors. RFX6 is a transcription factor essential for mouse β cell differentiation that is mutated in monogenic forms of neonatal diabetes. However, the expression and functional roles of RFX6 in human β cells, espe...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.11.010
更新日期：2014-12-24 00:00:00
abstract：:The mechanisms by which p53 suppresses tumor growth remain ill defined. In this issue of Cell Reports, Timofeev et al. (2013) and Valente et al. (2013) reveal context-dependent contributions of p53-dependent apoptosis to its tumor-suppressive function. ...
journal_title：Cell reports
pub_type： 评论,杂志文章
doi：10.1016/j.celrep.2013.05.011
更新日期：2013-05-30 00:00:00
abstract：:Working memory is mediated by the coordinated activation of frontal and parietal cortices occurring in the theta and alpha frequency ranges. Here, we test whether electrically stimulating frontal and parietal regions at the frequency of interaction is effective in modulating working memory. We identify working memory ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.10.072
更新日期：2019-11-26 00:00:00
abstract：:In mammals, the noncoding Xist RNA triggers transcriptional silencing of one of the two X chromosomes in female cells. Here, we report a genetic screen for silencing factors in X chromosome inactivation using haploid mouse embryonic stem cells (ESCs) that carry an engineered selectable reporter system. This system was...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.06.067
更新日期：2015-07-28 00:00:00
abstract：:Granule cells (GCs) of the cerebellar input layer express high-affinity δ GABAA subunit-containing GABAA receptors (δGABAARs) that respond to ambient GABA levels and context-dependent neuromodulators like steroids. We find that GC-specific deletion of δGABAA (cerebellar [cb] δ knockout [KO]) decreases tonic inhibition...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.108338
更新日期：2020-11-03 00:00:00
abstract：:Schwann cells (SCs) myelinate peripheral neurons to promote the rapid conduction of action potentials, and the process of myelination is known to be regulated by signals from axons to SCs. Given that SC mitochondria are one of the potential regulators of myelination, we investigated whether SC mitochondria are regulat...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.08.039
更新日期：2015-09-29 00:00:00
abstract：:Animal nervous systems remodel following stress. Although global stress-dependent changes are well documented, contributions of individual neuron remodeling events to animal behavior modification are challenging to study. In response to environmental insults, C. elegans become stress-resistant dauers. Dauer entry indu...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.108607
更新日期：2021-01-12 00:00:00
abstract：:Plasmodium parasites infect the liver and replicate inside hepatocytes before they invade erythrocytes and trigger clinical malaria. Analysis of host signaling pathways affected by liver-stage infection could provide critical insights into host-pathogen interactions and reveal targets for intervention. Using protein l...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2013.02.010
更新日期：2013-03-28 00:00:00
abstract：:Alzheimer's disease (AD) is the most common form of dementia, impairing cognitive and motor functions. One of the pathological hallmarks of AD is neuronal loss, which is not reflected in mouse models of AD. Therefore, the role of neuronal death is still uncertain. Here, we used a Drosophila AD model expressing a secre...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.11.098
更新日期：2018-12-26 00:00:00
abstract：:Polymorphisms that alter serotonin transporter SERT expression and functionality increase the risks for autism and psychiatric traits. Here, we investigate how SERT controls serotonin signaling in developing CNS in mice. SERT is transiently expressed in specific sets of glutamatergic neurons and uptakes extrasynaptic ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.12.033
更新日期：2015-01-20 00:00:00
abstract：:Protein-coding genes undergo a wide array of regulatory interactions with factors that engage non-coding regions. Open reading frames (ORFs), in contrast, are thought to be constrained by coding function, precluding a major role in gene regulation. Here, we explore Piwi-interacting (pi)RNA-mediated transgene silencing...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.02.009
更新日期：2018-02-27 00:00:00
abstract：:Altered physiological states require neuronal adaptation. In late pregnancy and lactation, a sub-population of the mouse hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons alters their behavior to synthesize and release met-enkephalin rather than dopamine. These neurons normally release dopamine to inhibit pr...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.01.067
更新日期：2019-02-12 00:00:00
abstract：:Translation of mRNAs in dendrites mediates synaptic plasticity, the probable cellular basis of learning and memory. Coordination of translational inhibitory and stimulatory mechanisms, as well as dendritic transport of mRNA, is necessary to ensure proper control of this local translation. Here, we find that the deaden...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2017.06.078
更新日期：2017-07-18 00:00:00
abstract：:The bacterial pathogen Listeria monocytogenes (Lm) capitalizes on natural killer (NK) cell production of regulatory interleukin (IL)-10 to establish severe systemic infections. Here, we identify regulators of this IL-10 secretion. We show that IL-18 signals to NK cells license their ability to produce IL-10. IL-18 act...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.04.106
更新日期：2018-05-29 00:00:00
abstract：:The regulation and functional roles of secreted coding and long noncoding RNAs (lncRNAs; >200 nt) are largely unknown. We previously showed that mutant KRAS colorectal cancer (CRC) cells release extracellular vesicles (EVs) containing distinct proteomes, microRNAs (miRNAs), and circular RNAs. Here, we comprehensively ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.09.054
更新日期：2018-10-16 00:00:00
abstract：:The endoplasmic reticulum (ER) unfolded protein response (UPR(er)) pathway plays an important role in helping pancreatic β cells to adapt their cellular responses to environmental cues and metabolic stress. Although altered UPR(er) gene expression appears in rodent and human type 2 diabetic (T2D) islets, the underlyin...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.03.079
更新日期：2016-05-03 00:00:00
abstract：:A two-step, automated, high-throughput RNAi silencing screen was used to identify host cell factors required during vaccinia virus infection. Validation and analysis of clustered hits revealed previously unknown processes during virus entry, including a mechanism for genome uncoating. Viral core proteins were found to...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2012.09.003
更新日期：2012-10-25 00:00:00
abstract：:The Fanconi anemia (FA) pathway is critically involved in the maintenance of hematopoietic stem cells and the suppression of carcinogenesis. A key FA protein, FANCD2, is monoubiquitinated and accumulates in chromatin in response to DNA interstrand crosslinks (ICLs), where it coordinates DNA repair through mechanisms t...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2014.04.005
更新日期：2014-05-22 00:00:00
abstract：:The dynamic interactions between synaptic excitation and inhibition (E/I) shape membrane potential fluctuations and determine patterns of neuronal outputs; however, the spatiotemporal organization of these interactions within a single cell is poorly understood. Here, we investigated the relationship between local syna...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.01.024
更新日期：2016-02-16 00:00:00
abstract：:The newest classes of anti-diabetic agents include sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor (GLP1R) agonists. The SGLT2 inhibitor dapagliflozin reduces glucotoxicity by glycosuria but elevates glucagon secretion. The GLP1R agonist liraglutide inhibits glucagon; therefore, ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2019.07.009
更新日期：2019-08-06 00:00:00
abstract：:Recent studies have elucidated the molecular mechanism of RORγT transcriptional regulation of Th17 differentiation and function. RORγT was initially identified as a transcription factor required for thymopoiesis by maintaining survival of CD4+CD8+ (DP) thymocytes. While RORγ antagonists are currently being developed t...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.11.073
更新日期：2016-12-20 00:00:00
abstract：:Innate immunity is central to the pathophysiology of neurodegenerative disorders, but it remains unclear why immunity is altered in the disease state and whether changes in immunity are a cause or a consequence of neuronal dysfunction. Here, we identify a molecular pathway that links innate immunity to age-dependent l...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2018.12.025
更新日期：2019-01-02 00:00:00
abstract：:CELF6 is a CELF-RNA-binding protein, and thus part of a protein family with roles in human disease; however, its mRNA targets in the brain are largely unknown. Using cross-linking immunoprecipitation and sequencing (CLIP-seq), we define its CNS targets, which are enriched for 3' UTRs in synaptic protein-coding genes. ...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2020.108531
更新日期：2020-12-22 00:00:00
abstract：:The transcription factor hepatic leukemia factor (HLF) is strongly expressed in hematopoietic stem cells (HSCs) and is thought to influence both HSC self-renewal and leukemogenesis. However, the physiological role of HLF in hematopoiesis and HSC function is unclear. Here, we report that mice lacking Hlf are viable wit...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2017.11.084
更新日期：2017-12-19 00:00:00
abstract：:Signal transducer and activator of transcription 3 (STAT3) is a transcription factor central to axon regrowth with an enigmatic ability to act in different subcellular regions independently of its transcriptional roles. However, its roles in mature CNS neurons remain unclear. Here, we show that along with nuclear tran...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2016.03.029
更新日期：2016-04-12 00:00:00
abstract：:Naturally acquired immunity to malaria develops only after years of repeated exposure to Plasmodium parasites. Despite the key role antibodies play in protection, the cellular processes underlying the slow acquisition of immunity remain unknown. Using mouse models, we show that severe malaria infection inhibits the es...
journal_title：Cell reports
pub_type： 杂志文章
doi：10.1016/j.celrep.2015.12.006
更新日期：2016-01-05 00:00:00
