Abstract:
:Scleroderma is an autoimmune rheumatic disorder accompanied by severe fibrosis in skin and other internal organs. During scleroderma progression, resident fibroblasts undergo activation and convert to α-smooth muscle actin (α-SMA) expressing myofibroblasts (MFBs) with increased capacity to synthesize collagens and fibrogenic components. Accordingly, MFBs are a major therapeutic target for fibrosis in scleroderma and treatment with blocking MFBs could produce anti-fibrotic effects. TLY012 is an engineered human TNF-related apoptosis-inducing ligand (TRAIL) which induces selective apoptosis in transformed cells expressing its cognate death receptors (DRs). Here we report that TLY012 selectively blocks activation of dermal fibroblasts and induces DR-mediated apoptosis in α-SMA+ MFBs through upregulated DR5 during its activation. In vivo, TLY012 reverses established skin fibrosis to near-normal skin architecture in mouse models of scleroderma. Thus, the TRAIL pathway plays a critical role in tissue remodeling and targeting upregulated DR5 in α-SMA+ MFBs is a viable therapy for fibrosis in scleroderma.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Park JS,Oh Y,Park YJ,Park O,Yang H,Slania S,Hummers LK,Shah AA,An HT,Jang J,Horton MR,Shin J,Dietz HC,Song E,Na DH,Park EJ,Kim K,Lee KC,Roschke VV,Hanes J,Pomper MG,Lee Sdoi
10.1038/s41467-019-09101-4subject
Has Abstractpub_date
2019-03-08 00:00:00pages
1128issue
1issn
2041-1723pii
10.1038/s41467-019-09101-4journal_volume
10pub_type
杂志文章abstract::N-methyl-D-aspartate receptors (NMDARs) play a central role in synaptic plasticity, learning and memory, and are implicated in various neuronal disorders. We synthesized a diffusible photochromic glutamate analogue, azobenzene-triazole-glutamate (ATG), which is specific for NMDARs and functions as a photoswitchable ag...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms9076
更新日期:2015-08-27 00:00:00
abstract::How do descending inputs from the brain control leg motor circuits to change how an animal walks? Conceptually, descending neurons are thought to function either as command-type neurons, in which a single type of descending neuron exerts a high-level control to elicit a coordinated change in motor output, or through a...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-19936-x
更新日期:2020-12-02 00:00:00
abstract::Collective cell migration mediates multiple tissue morphogenesis processes. Yet how multi-dimensional mesenchymal cell movements are coordinated remains mostly unknown. Here we report that coordinated mesenchymal cell migration during chicken feather elongation is accompanied by dynamic changes of bioelectric currents...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-07661-5
更新日期:2018-12-18 00:00:00
abstract::Laryngeal squamous cell carcinoma is a frequent and significant cause of morbidity and mortality. Here we explore the biological basis of this aggressive tumour, and identify two cell-cell adhesion genes as recurrently mutated in this malignancy. We first perform exome sequencing of four laryngeal carcinomas and their...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms3531
更新日期:2013-01-01 00:00:00
abstract::The circular photogalvanic effect (CPGE) is the part of a photocurrent that switches depending on the sense of circular polarization of the incident light. It has been consistently observed in systems without inversion symmetry and depends on non-universal material details. Here we find that in a class of Weyl semimet...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms15995
更新日期:2017-07-06 00:00:00
abstract::The Tie receptors with their Angiopoietin ligands act as regulators of angiogenesis and vessel maturation. Tie2 exerts its functions through its supposed endothelial-specific expression. Yet, Tie2 is also expressed at lower levels by pericytes and it has not been unravelled through which mechanisms pericyte Angiopoiet...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms16106
更新日期:2017-07-18 00:00:00
abstract::The liver parenchyma is composed of hepatocytes and bile duct epithelial cells (BECs). Controversy exists regarding the cellular origin of human liver parenchymal tissue generation during embryonic development, homeostasis or repair. Here we report the existence of a hepatobiliary hybrid progenitor (HHyP) population i...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-11266-x
更新日期:2019-07-26 00:00:00
abstract::The Earth's sole active carbonatite volcano, Oldoinyo Lengai (Tanzania), is presently erupting unique natrocarbonatite lavas that are characterized by Na- and K-bearing magmatic carbonates of nyerereite [Na2Ca(CO3)2] and gregoryite [(Na2,K2,Ca)CO3]. Contrarily, the vast majority of older, plutonic carbonatite occurren...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms3687
更新日期:2013-01-01 00:00:00
abstract::CD47 is a cell surface molecule that inhibits phagocytosis of cells that express it by binding to its receptor, SIRPα, on macrophages and other immune cells. CD47 is expressed at different levels by neoplastic and normal cells. Here, to reveal mechanisms by which different neoplastic cells generate this dominant 'don'...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms14802
更新日期:2017-04-05 00:00:00
abstract::Writing artificial logic and dynamic function into complex cellular background to achieve desired phenotypes or improved outputs calls for the development of new genetic tools as well as their innovative use. In this study, we present a sensor-regulator and RNAi-based bifunctional dynamic control network that can prov...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-018-05466-0
更新日期:2018-08-02 00:00:00
abstract::Maintenance of working memory is thought to involve the activity of prefrontal neuronal populations with strong recurrent connections. However, it was recently shown that distractors evoke a morphing of the prefrontal population code, even when memories are maintained throughout the delay. How can a morphing code main...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-12841-y
更新日期:2019-11-01 00:00:00
abstract::It is known that transient receptor potential ankyrin 1 (TRPA1) channels, expressed by nociceptors, contribute to neuropathic pain. Here we show that TRPA1 is also expressed in Schwann cells. We found that in mice with partial sciatic nerve ligation, TRPA1 silencing in nociceptors attenuated mechanical allodynia, with...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-01739-2
更新日期:2017-12-01 00:00:00
abstract::Understanding and extracting the full functions of single-molecule characteristics are key factors in the development of future device technologies, as well as in basic research on molecular electronics. Here we report a new methodology for realizing a three-dimensional (3D) dynamic probe of single-molecule conductanc...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms9465
更新日期:2015-10-06 00:00:00
abstract::Light propagating in tissue attains a spectrum that varies with location due to wavelength-dependent fluence attenuation, an effect that causes spectral corruption. Spectral corruption has limited the quantification accuracy of optical and optoacoustic spectroscopic methods, and impeded the goal of imaging blood oxyge...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms12121
更新日期:2016-06-30 00:00:00
abstract::Polyborylated organic compounds have been emerging as versatile building blocks in chemical synthesis. Here we report a selective cobalt-catalyzed deoxygenative 1,1,3-triborylation reaction of allylic ethers with pinacolborane to prepare 1,1,3-triborylalkane compounds. With naturally abundant and/or synthetic cinnamic...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-19039-7
更新日期:2020-10-15 00:00:00
abstract::Although kidney parenchymal tissue can be generated in vitro, reconstructing the complex vasculature of the kidney remains a daunting task. The molecular pathways that specify and sustain functional, phenotypic and structural heterogeneity of the kidney vasculature are unknown. Here, we employ high-throughput bulk and...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-12872-5
更新日期:2019-12-13 00:00:00
abstract::The practices of synthetic biology are being integrated into 'multiscale' designs enabling two-way communication across organic and inorganic information substrates in biological, digital and cyber-physical system integrations. Novel applications of 'bio-informational' engineering will arise in environmental monitorin...
journal_title:Nature communications
pub_type: 杂志文章,评审
doi:10.1038/s41467-020-20764-2
更新日期:2021-01-15 00:00:00
abstract::Rosemary extracts containing the phenolic diterpenes carnosic acid and its derivative carnosol are approved food additives used in an increasingly wide range of products to enhance shelf-life, thanks to their high anti-oxidant activity. We describe here the elucidation of the complete biosynthetic pathway of carnosic ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms12942
更新日期:2016-10-05 00:00:00
abstract::The turnover of messenger RNAs (mRNAs) is a key regulatory step of gene expression in eukaryotic cells. Due to the complexity of the mammalian degradation machinery, the contribution of decay factors to the directionality of mRNA decay is poorly understood. Here we characterize a molecular tool to interrogate mRNA tur...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms13691
更新日期:2016-12-05 00:00:00
abstract::Little is known about how archaeal viruses perturb the transcription machinery of their hosts. Here we provide the first example of an archaeo-viral transcription factor that directly targets the host RNA polymerase (RNAP) and efficiently represses its activity. ORF145 from the temperate Acidianus two-tailed virus (AT...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms13595
更新日期:2016-11-24 00:00:00
abstract::Ferroptosis is a newly defined form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides. Erastin, the ferroptosis activator, binds to voltage-dependent anion channels VDAC2 and VDCA3, but treatment with erastin can result in the degradation of the channels. Here, the author...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-14324-x
更新日期:2020-01-23 00:00:00
abstract::Neuronal reward valuations provide the physiological basis for economic behaviour. Yet, how such valuations are converted to economic decisions remains unclear. Here we show that the dorsolateral prefrontal cortex (DLPFC) implements a flexible value code based on object-specific valuations by single neurons. As monkey...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms12554
更新日期:2016-09-13 00:00:00
abstract::The divalent carbene carbon centre in cyclic (alkyl)(amino)carbenes (CAACs) is known to exhibit transition-metal-like insertion into E-H σ-bonds (E = H, N, Si, B, P, C, O) with formation of new, strong C-E and C-H bonds. Although subsequent transformations of the products represent an attractive strategy for metal-fre...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-08967-8
更新日期:2019-03-26 00:00:00
abstract::The original version of this Article contained an error in the last sentence of the second paragraph of the 'Atmospheric rarefaction effects' section of the Results, which incorrectly read 'The other one emulates the rarefied, CO2-rich Martian atmosphere (μ♂ = 1.3 × 10-5 N s m-2) at 6.9 mbar and 210 K, which gives ρ♂ ...
journal_title:Nature communications
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41467-018-04545-6
更新日期:2018-05-21 00:00:00
abstract::In germinal centres (GC) mature B cells undergo intense proliferation and immunoglobulin gene modification before they differentiate into memory B cells or long-lived plasma cells (PC). GC B-cell-to-PC transition involves a major transcriptional switch that promotes a halt in cell proliferation and the production of s...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms16067
更新日期:2017-07-05 00:00:00
abstract::While main group elements have four valence orbitals accessible for bonding, quadruple bonding to main group elements is extremely rare. Here we report that main group element boron is able to form quadruple bonding interactions with iron in the BFe(CO)3- anion complex, which has been revealed by quantum chemical inve...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-019-12767-5
更新日期:2019-10-17 00:00:00
abstract::The abundance of sodium resources indicates the potential of sodium-ion batteries as emerging energy storage devices. However, the practical application of sodium-ion batteries is hindered by the limited electrochemical performance of electrode materials, especially at the anode side. Here, we identify alkaline earth ...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-017-00211-5
更新日期:2017-09-06 00:00:00
abstract::Despite rapid advances in genome engineering technologies, inserting genes into precise locations in the human genome remains an outstanding problem. It has been suggested that site-specific recombinases can be adapted towards use as transgene delivery vectors. The specificity of recombinases can be altered either wit...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms3509
更新日期:2013-01-01 00:00:00
abstract::The continued convergence of electronics and photonics on the chip scale can benefit from the voltage control of optical polarization for applications in communications, signal processing and sensing. It is challenging, however, to electrically manipulate the polarization state of light in planar optical waveguides. H...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/ncomms6337
更新日期:2014-11-12 00:00:00
abstract::Microbial biofilm formation on indwelling medical devices causes persistent infections that cannot be cured with conventional antibiotics. To address this unmet challenge, we engineer tunable active surface topographies with micron-sized pillars that can beat at a programmable frequency and force level in an electroma...
journal_title:Nature communications
pub_type: 杂志文章
doi:10.1038/s41467-020-16055-5
更新日期:2020-05-05 00:00:00