PAK proteins and YAP-1 signalling downstream of integrin beta-1 in myofibroblasts promote liver fibrosis.

Abstract:

:Fibrosis due to extracellular matrix (ECM) secretion from myofibroblasts complicates many chronic liver diseases causing scarring and organ failure. Integrin-dependent interaction with scar ECM promotes pro-fibrotic features. However, the pathological intracellular mechanism in liver myofibroblasts is not completely understood, and further insight could enable therapeutic efforts to reverse fibrosis. Here, we show that integrin beta-1, capable of binding integrin alpha-11, regulates the pro-fibrotic phenotype of myofibroblasts. Integrin beta-1 expression is upregulated in pro-fibrotic myofibroblasts in vivo and is required in vitro for production of fibrotic ECM components, myofibroblast proliferation, migration and contraction. Serine/threonine-protein kinase proteins, also known as P21-activated kinase (PAK), and the mechanosensitive factor, Yes-associated protein 1 (YAP-1) are core mediators of pro-fibrotic integrin beta-1 signalling, with YAP-1 capable of perpetuating integrin beta-1 expression. Pharmacological inhibition of either pathway in vivo attenuates liver fibrosis. PAK protein inhibition, in particular, markedly inactivates the pro-fibrotic myofibroblast phenotype, limits scarring from different hepatic insults and represents a new tractable therapeutic target for treating liver fibrosis.

journal_name

Nat Commun

journal_title

Nature communications

authors

Martin K,Pritchett J,Llewellyn J,Mullan AF,Athwal VS,Dobie R,Harvey E,Zeef L,Farrow S,Streuli C,Henderson NC,Friedman SL,Hanley NA,Piper Hanley K

doi

10.1038/ncomms12502

subject

Has Abstract

pub_date

2016-08-18 00:00:00

pages

12502

issn

2041-1723

pii

ncomms12502

journal_volume

7

pub_type

杂志文章
  • Quantifying net loss of global mangrove carbon stocks from 20 years of land cover change.

    abstract::Mangrove forests hold some of the highest densities of carbon recorded in any ecosystem, but have experienced widespread deforestation through conversion to aquaculture and agriculture. Alongside deforestation, mangroves have shown simultaneous natural expansion in some parts of the world, and considerable investments...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-18118-z

    authors: Richards DR,Thompson BS,Wijedasa L

    更新日期:2020-08-26 00:00:00

  • Calculating with light using a chip-scale all-optical abacus.

    abstract::Machines that simultaneously process and store multistate data at one and the same location can provide a new class of fast, powerful and efficient general-purpose computers. We demonstrate the central element of an all-optical calculator, a photonic abacus, which provides multistate compute-and-store operation by int...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-017-01506-3

    authors: Feldmann J,Stegmaier M,Gruhler N,Ríos C,Bhaskaran H,Wright CD,Pernice WHP

    更新日期:2017-11-02 00:00:00

  • Rapid expansion of Treg cells protects from collateral colitis following a viral trigger.

    abstract::Foxp3+ regulatory T (Treg) cells are essential for maintaining peripheral tolerance and preventing autoimmunity. While genetic factors may predispose for autoimmunity, additional environmental triggers, such as viral infections, are usually required to initiate the onset of disease. Here, we show that viral infection ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-15309-6

    authors: Schorer M,Lambert K,Rakebrandt N,Rost F,Kao KC,Yermanos A,Spörri R,Oderbolz J,Raeber ME,Keller CW,Lünemann JD,Rogler G,Boyman O,Oxenius A,Joller N

    更新日期:2020-03-23 00:00:00

  • Direct visualization of current-induced spin accumulation in topological insulators.

    abstract::Charge-to-spin conversion in various materials is the key for the fundamental understanding of spin-orbitronics and efficient magnetization manipulation. Here we report the direct spatial imaging of current-induced spin accumulation at the channel edges of Bi2Se3 and BiSbTeSe2 topological insulators as well as Pt by a...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-04939-6

    authors: Liu Y,Besbas J,Wang Y,He P,Chen M,Zhu D,Wu Y,Lee JM,Wang L,Moon J,Koirala N,Oh S,Yang H

    更新日期:2018-06-27 00:00:00

  • Split spawning realigns coral reproduction with optimal environmental windows.

    abstract::Split spawning in coral populations occurs when gamete maturation and mass spawning are split over two consecutive months. While split spawning has been observed at many reefs, little is known about the frequency and significance of these events. Here we show that split spawning occurred frequently and predictably ove...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-03175-2

    authors: Foster T,Heyward AJ,Gilmour JP

    更新日期:2018-02-19 00:00:00

  • Plasmodium myosin A drives parasite invasion by an atypical force generating mechanism.

    abstract::Plasmodium parasites are obligate intracellular protozoa and causative agents of malaria, responsible for half a million deaths each year. The lifecycle progression of the parasite is reliant on cell motility, a process driven by myosin A, an unconventional single-headed class XIV molecular motor. Here we demonstrate ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-11120-0

    authors: Robert-Paganin J,Robblee JP,Auguin D,Blake TCA,Bookwalter CS,Krementsova EB,Moussaoui D,Previs MJ,Jousset G,Baum J,Trybus KM,Houdusse A

    更新日期:2019-07-23 00:00:00

  • Nanoelectromechanical coupling in fullerene peapods probed by resonant electrical transport experiments.

    abstract::Fullerene peapods, which are carbon nanotubes encapsulating fullerene molecules, can offer enhanced functionality with respect to empty nanotubes. Their prospective applications include, for example, data storage devices, single-electron transistors and spin-qubit arrays for quantum computing. However, the present inc...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms1034

    authors: Utko P,Ferone R,Krive IV,Shekhter RI,Jonson M,Monthioux M,Noé L,Nygård J

    更新日期:2010-07-13 00:00:00

  • Colloidal interactions and unusual crystallization versus de-mixing of elastic multipoles formed by gold mesoflowers.

    abstract::Colloidal interactions in nematic liquid crystals can be described as interactions between elastic multipoles that depend on particle shape, topology, chirality, boundary conditions and induced topological defects. Here, we describe a nematic colloidal system consisting of mesostructures of gold capable of inducing el...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-019-14031-2

    authors: Yuan Y,Tasinkevych M,Smalyukh II

    更新日期:2020-01-10 00:00:00

  • Massive mining of publicly available RNA-seq data from human and mouse.

    abstract::RNA sequencing (RNA-seq) is the leading technology for genome-wide transcript quantification. However, publicly available RNA-seq data is currently provided mostly in raw form, a significant barrier for global and integrative retrospective analyses. ARCHS4 is a web resource that makes the majority of published RNA-seq...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-03751-6

    authors: Lachmann A,Torre D,Keenan AB,Jagodnik KM,Lee HJ,Wang L,Silverstein MC,Ma'ayan A

    更新日期:2018-04-10 00:00:00

  • Thermal transport in phononic crystals and the observation of coherent phonon scattering at room temperature.

    abstract::Large reductions in the thermal conductivity of thin silicon membranes have been demonstrated in various porous structures. However, the role of coherent boundary scattering in such structures has become a matter of some debate. Here we report on the first experimental observation of coherent phonon boundary scatterin...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms8228

    authors: Alaie S,Goettler DF,Su M,Leseman ZC,Reinke CM,El-Kady I

    更新日期:2015-06-24 00:00:00

  • Author Correction: A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Nature communications

    pub_type: 已发布勘误

    doi:10.1038/s41467-019-10951-1

    authors: International Multiple Sclerosis Genetics Consortium.

    更新日期:2019-07-01 00:00:00

  • Bcl9 and Pygo synergise downstream of Apc to effect intestinal neoplasia in FAP mouse models.

    abstract::Bcl9 and Pygo are Wnt enhanceosome components that effect β-catenin-dependent transcription. Whether they mediate β-catenin-dependent neoplasia is unclear. Here we assess their roles in intestinal tumourigenesis initiated by Apc loss-of-function (ApcMin), or by Apc1322T encoding a partially-functional Apc truncation c...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-08164-z

    authors: Mieszczanek J,van Tienen LM,Ibrahim AEK,Winton DJ,Bienz M

    更新日期:2019-02-13 00:00:00

  • Design of highly efficient deep-blue organic afterglow through guest sensitization and matrices rigidification.

    abstract::Blue/deep-blue emission is crucial for organic optoelectronics but remains a formidable challenge in organic afterglow due to the difficulties in populating and stabilizing the high-energy triplet excited states. Here, a facile strategy to realize the efficient deep-blue organic afterglow is proposed via host molecule...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-18572-9

    authors: Xu S,Wang W,Li H,Zhang J,Chen R,Wang S,Zheng C,Xing G,Song C,Huang W

    更新日期:2020-09-23 00:00:00

  • Antidromic-rectifying gap junctions amplify chemical transmission at functionally mixed electrical-chemical synapses.

    abstract::Neurons communicate through chemical synapses and electrical synapses (gap junctions). Although these two types of synapses often coexist between neurons, little is known about whether they interact, and whether any interactions between them are important to controlling synaptic strength and circuit functions. By stud...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms14818

    authors: Liu P,Chen B,Mailler R,Wang ZW

    更新日期:2017-03-20 00:00:00

  • Effect of hydrogen on the integrity of aluminium-oxide interface at elevated temperatures.

    abstract::Hydrogen can facilitate the detachment of protective oxide layer off metals and alloys. The degradation is usually exacerbated at elevated temperatures in many industrial applications; however, its origin remains poorly understood. Here by heating hydrogenated aluminium inside an environmental transmission electron mi...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms14564

    authors: Li M,Xie DG,Ma E,Li J,Zhang XX,Shan ZW

    更新日期:2017-02-20 00:00:00

  • Tailoring manganese oxide with atomic precision to increase surface site availability for oxygen reduction catalysis.

    abstract::Controlling the structure of catalysts at the atomic level provides an opportunity to establish detailed understanding of the catalytic form-to-function and realize new, non-equilibrium catalytic structures. Here, advanced thin-film deposition is used to control the atomic structure of La2/3Sr1/3MnO3, a well-known cat...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-06503-8

    authors: Eom CJ,Kuo DY,Adamo C,Moon EJ,May SJ,Crumlin EJ,Schlom DG,Suntivich J

    更新日期:2018-10-02 00:00:00

  • Genome-wide association study implicates NDST3 in schizophrenia and bipolar disorder.

    abstract::Schizophrenia and bipolar disorder are major psychiatric disorders with high heritability and overlapping genetic variance. Here we perform a genome-wide association study in an ethnically homogeneous cohort of 904 schizophrenia cases and 1,640 controls drawn from the Ashkenazi Jewish population. We identify a novel g...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms3739

    authors: Lencz T,Guha S,Liu C,Rosenfeld J,Mukherjee S,DeRosse P,John M,Cheng L,Zhang C,Badner JA,Ikeda M,Iwata N,Cichon S,Rietschel M,Nöthen MM,Cheng AT,Hodgkinson C,Yuan Q,Kane JM,Lee AT,Pisanté A,Gregersen PK,Pe'er I

    更新日期:2013-01-01 00:00:00

  • Power laws in pressure-induced structural change of glasses.

    abstract::Many glasses exhibit fractional power law (FPL) between the mean atomic volume va and the first diffraction peak position q1, i.e. [Formula: see text] with d ≃ 2.5 deviating from the space dimension D = 3, under compression or composition change. What structural change causes such FPL and whether the FPL and d are uni...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-15583-4

    authors: Zhang H,Qiao K,Han Y

    更新日期:2020-04-24 00:00:00

  • CMOS-based carbon nanotube pass-transistor logic integrated circuits.

    abstract::Field-effect transistors based on carbon nanotubes have been shown to be faster and less energy consuming than their silicon counterparts. However, ensuring these advantages are maintained for integrated circuits is a challenge. Here we demonstrate that a significant reduction in the use of field-effect transistors ca...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms1682

    authors: Ding L,Zhang Z,Liang S,Pei T,Wang S,Li Y,Zhou W,Liu J,Peng LM

    更新日期:2012-02-14 00:00:00

  • Kinetic asymmetry allows macromolecular catalysts to drive an information ratchet.

    abstract::Molecular machines carry out their function by equilibrium mechanical motions in environments that are far from thermodynamic equilibrium. The mechanically equilibrated character of the trajectories of the macromolecule has allowed development of a powerful theoretical description, reminiscent of Onsager's trajectory ...

    journal_title:Nature communications

    pub_type: 杂志文章,评审

    doi:10.1038/s41467-019-11402-7

    authors: Astumian RD

    更新日期:2019-08-23 00:00:00

  • Publisher Correction: Reconciling qualitative, abstract, and scalable modeling of biological networks.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Nature communications

    pub_type: 已发布勘误

    doi:10.1038/s41467-020-18766-1

    authors: Paulevé L,Kolčák J,Chatain T,Haar S

    更新日期:2020-09-24 00:00:00

  • Multiscale real time and high sensitivity ion detection with complementary organic electrochemical transistors amplifier.

    abstract::Ions are ubiquitous biological regulators playing a key role for vital processes in animals and plants. The combined detection of ion concentration and real-time monitoring of small variations with respect to the resting conditions is a multiscale functionality providing important information on health states. This mu...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-17547-0

    authors: Romele P,Gkoupidenis P,Koutsouras DA,Lieberth K,Kovács-Vajna ZM,Blom PWM,Torricelli F

    更新日期:2020-07-27 00:00:00

  • Basal lamina remodeling at the skeletal muscle stem cell niche mediates stem cell self-renewal.

    abstract::A central question in stem cell biology is the relationship between stem cells and their niche. Although previous reports have uncovered how signaling molecules released by niche cells support stem cell function, the role of the extra-cellular matrix (ECM) within the niche is unclear. Here, we show that upon activatio...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-03425-3

    authors: Rayagiri SS,Ranaldi D,Raven A,Mohamad Azhar NIF,Lefebvre O,Zammit PS,Borycki AG

    更新日期:2018-03-14 00:00:00

  • Optimized design of single-cell RNA sequencing experiments for cell-type-specific eQTL analysis.

    abstract::Single-cell RNA-sequencing (scRNA-Seq) is a compelling approach to directly and simultaneously measure cellular composition and state, which can otherwise only be estimated by applying deconvolution methods to bulk RNA-Seq estimates. However, it has not yet become a widely used tool in population-scale analyses, due t...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-19365-w

    authors: Mandric I,Schwarz T,Majumdar A,Hou K,Briscoe L,Perez R,Subramaniam M,Hafemeister C,Satija R,Ye CJ,Pasaniuc B,Halperin E

    更新日期:2020-10-30 00:00:00

  • Macromolecular and electrical coupling between inner hair cells in the rodent cochlea.

    abstract::Inner hair cells (IHCs) are the primary receptors for hearing. They are housed in the cochlea and convey sound information to the brain via synapses with the auditory nerve. IHCs have been thought to be electrically and metabolically independent from each other. We report that, upon developmental maturation, in mice 3...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-020-17003-z

    authors: Jean P,Anttonen T,Michanski S,de Diego AMG,Steyer AM,Neef A,Oestreicher D,Kroll J,Nardis C,Pangršič T,Möbius W,Ashmore J,Wichmann C,Moser T

    更新日期:2020-06-25 00:00:00

  • Mondo complexes regulate TFEB via TOR inhibition to promote longevity in response to gonadal signals.

    abstract::Germline removal provokes longevity in several species and shifts resources towards survival and repair. Several Caenorhabditis elegans transcription factors regulate longevity arising from germline removal; yet, how they work together is unknown. Here we identify a Myc-like HLH transcription factor network comprised ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms10944

    authors: Nakamura S,Karalay Ö,Jäger PS,Horikawa M,Klein C,Nakamura K,Latza C,Templer SE,Dieterich C,Antebi A

    更新日期:2016-03-22 00:00:00

  • The central role of EED in the orchestration of polycomb group complexes.

    abstract::Polycomb repressive complexes 1 and 2 (PRC1 and 2) play a critical role in the epigenetic regulation of transcription during cellular differentiation, stem cell pluripotency and neoplastic progression. Here we show that the polycomb group protein EED, a core component of PRC2, physically interacts with and functions a...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms4127

    authors: Cao Q,Wang X,Zhao M,Yang R,Malik R,Qiao Y,Poliakov A,Yocum AK,Li Y,Chen W,Cao X,Jiang X,Dahiya A,Harris C,Feng FY,Kalantry S,Qin ZS,Dhanasekaran SM,Chinnaiyan AM

    更新日期:2014-01-01 00:00:00

  • Subclonal mutation selection in mouse lymphomagenesis identifies known cancer loci and suggests novel candidates.

    abstract::Determining whether recurrent but rare cancer mutations are bona fide driver mutations remains a bottleneck in cancer research. Here we present the most comprehensive analysis of murine leukemia virus-driven lymphomagenesis produced to date, sequencing 700,000 mutations from >500 malignancies collected at time points ...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/s41467-018-05069-9

    authors: Webster P,Dawes JC,Dewchand H,Takacs K,Iadarola B,Bolt BJ,Caceres JJ,Kaczor J,Dharmalingam G,Dore M,Game L,Adejumo T,Elliott J,Naresh K,Karimi M,Rekopoulou K,Tan G,Paccanaro A,Uren AG

    更新日期:2018-07-09 00:00:00

  • Quantum spin Hall phase in 2D trigonal lattice.

    abstract::The quantum spin Hall (QSH) phase is an exotic phenomena in condensed-matter physics. Here we show that a minimal basis of three orbitals (s, px, py) is required to produce a QSH phase via nearest-neighbour hopping in a two-dimensional trigonal lattice. Tight-binding model analyses and calculations show that the QSH p...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms12746

    authors: Wang ZF,Jin KH,Liu F

    更新日期:2016-09-07 00:00:00

  • Developmental genetic bases behind the independent origin of the tympanic membrane in mammals and diapsids.

    abstract::The amniote middle ear is a classical example of the evolutionary novelty. Although paleontological evidence supports the view that mammals and diapsids (modern reptiles and birds) independently acquired the middle ear after divergence from their common ancestor, the developmental bases of these transformations remain...

    journal_title:Nature communications

    pub_type: 杂志文章

    doi:10.1038/ncomms7853

    authors: Kitazawa T,Takechi M,Hirasawa T,Adachi N,Narboux-Nême N,Kume H,Maeda K,Hirai T,Miyagawa-Tomita S,Kurihara Y,Hitomi J,Levi G,Kuratani S,Kurihara H

    更新日期:2015-04-22 00:00:00