Coagulation cascade proteases and tissue fibrosis.

Abstract:

:Fibrotic disorders of the liver, kidney and lung are associated with excessive deposition of extracellular matrix proteins and ongoing coagulation-cascade activity. In addition to their critical roles in blood coagulation, thrombin and the immediate upstream coagulation proteases, Factors Xa and VIIa, influence numerous cellular responses that may play critical roles in subsequent inflammatory and tissue repair processes in vascular and extravascular compartments. The cellular effects of these proteases are mediated via proteolytic activation of a novel family of cell-surface receptors, the protease-activated receptors (PAR-1, -2, -3 and -4). Although thrombin is capable of activating PAR-1, -3 and -4, there is accumulating in vitro evidence that the profibrotic effects of thrombin are predominantly mediated via PAR-1. Factor Xa is capable of activating PAR-1 and PAR-2, but its mitogenic effects for fibroblasts are similarly mediated via PAR-1. These proteases do not exert their profibrotic effects directly, but act via the induction of potent fibrogenic mediators, such as platelet-derived growth factor and connective tissue growth factor. In vivo studies using proteolytic inhibitors, PAR-1 antagonists and PAR-1-deficient mice have provided evidence that coagulation proteases play a key role in tissue inflammation and in a number of vascular pathologies associated with hyperproliferation of smooth muscle cells. More recently, coagulation proteases have also been shown to play a role in the pathogenesis of fibrosis but the relative contribution of their cellular versus their procoagulant effects awaits urgent evaluation in vivo. These studies will be informative in determining the potential application of PAR-1 antagonists as antifibrotic agents.

journal_name

Biochem Soc Trans

authors

Chambers RC,Laurent GJ

doi

10.1042/

keywords:

subject

Has Abstract

pub_date

2002-04-01 00:00:00

pages

194-200

issue

2

eissn

0300-5127

issn

1470-8752

journal_volume

30

pub_type

杂志文章,评审
  • Snf1 protein kinase: a key player in the response to cellular stress in yeast.

    abstract::Sucrose non-fermenting 1 (Snf1) protein kinase, a yeast homologue of mammalian AMP-activated protein kinase, plays a main role in transcriptional activation and repression of gene expression. In addition, Snf1 kinase has a broad role in the cellular response to several forms of stress, such as nutrient limitation, sal...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/bst0310178

    authors: Sanz P

    更新日期:2003-02-01 00:00:00

  • Mechanisms of hormone-induced desensitization of adenylate cyclase.

    abstract::Luteinizing hormone (LH) interacts with its plasma membrane receptor to activate the formation of cyclic AMP via the regulatory GTP binding protein (Gs). This is followed by a desensitization of that same hormonal response which is caused by an uncoupling of the LH receptor from Gs. The coupling between Gs and the ade...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/bst0170633

    authors: Cooke BA,Platts EA,Abayasekera DR,Rose MP

    更新日期:1989-08-01 00:00:00

  • Rho-ROCK signaling regulates tumor-microenvironment interactions.

    abstract::Reciprocal biochemical and biophysical interactions between tumor cells, stromal cells and the extracellular matrix (ECM) result in a unique tumor microenvironment that determines disease outcome. The cellular component of the tumor microenvironment contributes to tumor growth by providing nutrients, assisting in the ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20180334

    authors: Johan MZ,Samuel MS

    更新日期:2019-02-28 00:00:00

  • Emerging role of Alzheimer's disease-associated ubiquilin-1 in protein aggregation.

    abstract::Abnormal protein aggregation and intracellular or extracellular accumulation of misfolded and aggregated proteins are key events in the pathogenesis of different neurodegenerative diseases. Furthermore, endoplasmic reticulum stress and impairment of the ubiquitin-proteasome system probably contribute to neurodegenerat...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0380150

    authors: Haapasalo A,Viswanathan J,Bertram L,Soininen H,Tanzi RE,Hiltunen M

    更新日期:2010-02-01 00:00:00

  • Recycling domains in plant cell morphogenesis: small GTPase effectors, plasma membrane signalling and the exocyst.

    abstract::The Rho/Rop small GTPase regulatory module is central for initiating exocytotically ACDs (active cortical domains) in plant cell cortex, and a growing array of Rop regulators and effectors are being discovered in plants. Structural membrane phospholipids are important constituents of cells as well as signals, and phos...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0380723

    authors: Zárský V,Potocký M

    更新日期:2010-04-01 00:00:00

  • Modulation of signal-transduction pathways by chemopreventive agents.

    abstract::For a disease such as cancer, where a number of alterations to normal cell function accumulate over time, there are several opportunities to inhibit, slow down or even reverse the process. Many of the changes which drive the disease process occur in cell-signalling pathways that regulate proliferation and apoptosis. A...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/bst0280007

    authors: Manson MM,Holloway KA,Howells LM,Hudson EA,Plummer SM,Squires MS,Prigent SA

    更新日期:2000-02-01 00:00:00

  • Marine glycosaminoglycan-like carbohydrates as potential drug candidates for infectious disease.

    abstract::Glycosaminoglycans (GAGs), present in the extracellular matrix, are exploited by numerous, distinct microbes for cellular attachment, adhesion, invasion and evasion of the host immune system. Glycosaminoglycans, including the widely used, clinical anticoagulant heparin and semi-synthetic analogues thereof, have been r...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20170404

    authors: Mycroft-West CJ,Yates EA,Skidmore MA

    更新日期:2018-08-20 00:00:00

  • Allosteric modulators of metabotropic glutamate receptors: lessons learnt from mGlu1, mGlu2 and mGlu5 potentiators and antagonists.

    abstract::Although relatively few G-protein-coupled receptors are Class C, in recent years, this small family of receptors has become a focal point for the discovery of new and exciting allosteric modulators. The mGlu (metabotropic glutamate) receptors are illustrative in the discovery of both positive and/or negative allosteri...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0320881

    authors: Johnson MP,Nisenbaum ES,Large TH,Emkey R,Baez M,Kingston AE

    更新日期:2004-11-01 00:00:00

  • Polyunsaturated fatty acid-specific elongation enzymes.

    abstract::We have isolated a novel gene (GLELO) from Mortierella alpina and its homologue (CEELO1) from Caenorhabditis elegans and demonstrate the involvement of their encoded proteins in the elongation of C(18) polyunsaturated fatty acids. ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:

    authors: Das T,Thurmond JM,Bobik E,Leonard AE,Parker-Barnes JM,Huang YS,Mukerji P

    更新日期:2000-12-01 00:00:00

  • Virtual screening: a real screening complement to high-throughput screening.

    abstract::Virtual screening is being routinely used as an integral part of today's hit-identification strategies for, on one hand, prioritizing large corporate screening collections and, on the other hand, to extend the scope of screening to external databases. A brief description of the essential elements required for virtual ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/bst0300797

    authors: Mestres J

    更新日期:2002-08-01 00:00:00

  • EPR experiments to elucidate the structure of the ready and unready states of the [NiFe] hydrogenase of Desulfovibrio vulgaris Miyazaki F.

    abstract::Isolation and purification of the [NiFe] hydrogenase of Desulfovibrio vulgaris Miyazaki F under aerobic conditions leads to a mixture of two states, Ni-A (unready) and Ni-B (ready). The two states are distinguished by different activation times and different EPR spectra. HYSCORE and ENDOR data and DFT calculations sho...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0330007

    authors: van Gastel M,Fichtner C,Neese F,Lubitz W

    更新日期:2005-02-01 00:00:00

  • The third extracellular loop of G-protein-coupled receptors: more than just a linker between two important transmembrane helices.

    abstract::GPCRs (G-protein-coupled receptors) are a large family of structurally related proteins, which mediate their effects by coupling with G-proteins. Despite responding to a range of very diverse stimuli, these receptors exhibit a conserved tertiary structure comprising a bundle of seven TM (transmembrane) helices linked ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0321048

    authors: Lawson Z,Wheatley M

    更新日期:2004-12-01 00:00:00

  • BMP9 is a potential therapeutic agent for use in oral and maxillofacial bone tissue engineering.

    abstract::Oral and maxillofacial surgery is often challenging due to defective bone healing owing to the microbial environment of the oral cavity, the additional involvement of teeth and esthetic concerns. Insufficient bone volume as a consequence of aging and some oral and maxillofacial surgical procedures, such as tumor resec...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST20200376

    authors: Liu L,Chen Y,Song D,Huang D

    更新日期:2020-06-30 00:00:00

  • Solid-state NMR spectroscopy for characterization of RNA and RNP complexes.

    abstract::Ribonucleic acids are driving a multitude of biological processes where they act alone or in complex with proteins (ribonucleoproteins, RNP). To understand these processes both structural and mechanistic information about RNA is necessary. Due to their conformational plasticity RNA pose a challenge for mainstream stru...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST20191080

    authors: Sreemantula AK,Marchanka A

    更新日期:2020-06-30 00:00:00

  • Effects of intra-gene fitness interactions on the benefit of sexual recombination.

    abstract::Whereas spontaneous point mutation operates on nucleotides individually, sexual recombination manipulates the set of nucleotides within an allele as an essentially particulate unit. In principle, these two different scales of variation enable selection to follow fitness gradients in two different spaces: in nucleotide...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0340560

    authors: Watson RA,Weinreich DM,Wakeley J

    更新日期:2006-08-01 00:00:00

  • Placental mTOR links maternal nutrient availability to fetal growth.

    abstract::The mTOR (mammalian target of rapamycin) signalling pathway functions as a nutrient sensor, both in individual cells and, more globally, in organs such as the fat body in Drosophila and the hypothalamus in the rat. The activity of placental amino acid transporters is decreased in IUGR (intrauterine growth restriction)...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0370295

    authors: Roos S,Powell TL,Jansson T

    更新日期:2009-02-01 00:00:00

  • Computational studies of Family A and Family B GPCRs.

    abstract::A full picture of the similarities between Family A and Family B GPCRs (G-protein coupled receptors) has been frustrated by the lack of clear homology between the respective sequences. Here, we review previous computational studies on GPCR dimerization in which the putative dimerization interfaces have been analysed u...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0350749

    authors: Vohra S,Chintapalli SV,Illingworth CJ,Reeves PJ,Mullineaux PM,Clark HS,Dean MK,Upton GJ,Reynolds CA

    更新日期:2007-08-01 00:00:00

  • CRISPR base editing applications for identifying cancer-driving mutations.

    abstract::CRISPR base editing technology is a promising genome editing tool as (i) it does not require a DNA template to introduce mutations and (ii) it avoids creating DNA double-strand breaks, which can lead to unintended chromosomal alterations or elicit an unwanted DNA damage response. Given many cancers originate from poin...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST20200550

    authors: Pal M,Herold MJ

    更新日期:2021-01-15 00:00:00

  • Red, yellow, green go!--A novel tool for microscopic segregation of secretory vesicle pools according to their age.

    abstract::Large dense-core vesicles (LDCVs) were labelled in cultured bovine adrenal chromaffin cells expressing fluorescent chimaeric 'cargo' proteins that were targeted to these secretory vesicles. When the cells were stimulated with nicotine 48 h after transduction, the fractional loss of fluorescent LDCVs was much greater t...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/bst0310851

    authors: Wiegand UK,Duncan RR,Greaves J,Chow RH,Shipston MJ,Apps DK

    更新日期:2003-08-01 00:00:00

  • Non-genomic progesterone signalling and its non-canonical receptor.

    abstract::The steroid hormone progesterone regulates many critical aspects of vertebrate physiology. The nuclear receptor for progesterone functions as a ligand-activated transcription factor, directly regulating gene expression. This type of signalling is referred to as the 'genomic' pathway. Nevertheless, progesterone also st...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST20110638

    authors: Moussatche P,Lyons TJ

    更新日期:2012-02-01 00:00:00

  • Specificity and selectivity in post-translational biotin addition.

    abstract::Biotin, which serves as a carboxyl group carrier in reactions catalyzed by biotin-dependent carboxylases, is essential for life in most organisms. To function in carboxylate transfer, the vitamin must be post-translationally linked to a specific lysine residue on the biotin carboxyl carrier (BCC) of a carboxylase in a...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20180425

    authors: Beckett D

    更新日期:2018-12-17 00:00:00

  • Solid-state NMR spectroscopy as a tool for drug design: from membrane-embedded targets to amyloid fibrils.

    abstract::Structure-based design has gained credibility as a valuable component of the modern drug discovery process. The technique of SSNMR (solid-state NMR) promises to be a useful counterpart to the conventional experimental techniques of X-ray crystallography and solution-state NMR for providing structural features of drug ...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0350985

    authors: Middleton DA

    更新日期:2007-11-01 00:00:00

  • Exosomes as a novel way of interneuronal communication.

    abstract::Exosomes are small extracellular vesicles which stem from endosomes fusing with the plasma membrane; they contain lipids, proteins and RNAs that are able to modify receiving cells. Functioning of the brain relies on synapses, and certain patterns of synaptic activity can change the strength of responses at sparse grou...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20120266

    authors: Chivet M,Javalet C,Hemming F,Pernet-Gallay K,Laulagnier K,Fraboulet S,Sadoul R

    更新日期:2013-02-01 00:00:00

  • A PLCdelta1-binding protein, p122RhoGAP, is localized in focal adhesions.

    abstract::We have investigated the cellular distribution of p122RhoGAP, a GTPase-activating protein of Rho small GTPase and an activator of phospholipase C-delta(1). Immunofluorescence studies demonstrated that endogenous p122 is localized at the tips of actin stress fibres and co-localizes with vinculin in normal rat kidney ce...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST0321107

    authors: Kawai K,Yamaga M,Iwamae Y,Kiyota M,Kamata H,Hirata H,Homma Y,Yagisawa H

    更新日期:2004-12-01 00:00:00

  • Highly glycosylated tumour antigens: interactions with the immune system.

    abstract::A common phenotypic change in cancer is a dramatic transformation of cellular glycosylation. Functional studies of particular tumour-associated oligosaccharides are difficult to interpret conclusively, but carbohydrate-binding proteins are likely to contribute to progression of the tumour. This review discusses the po...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0390388

    authors: Saeland E,van Kooyk Y

    更新日期:2011-01-01 00:00:00

  • The furanosidic scaffold of d-ribose: a milestone for cell life.

    abstract::The recruitment of the furanosidic scaffold of ribose as the crucial step for nucleotides and then for nucleic acids synthesis is presented. Based on the view that the selection of molecules to be used for relevant metabolic purposes must favor structurally well-defined molecules, the inadequacy of ribose as a prefere...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST20190749

    authors: Del-Corso A,Cappiello M,Moschini R,Balestri F,Mura U,Ipata PL

    更新日期:2019-12-20 00:00:00

  • The evolutionary dynamics of venom toxins made by insects and other animals.

    abstract::Animal venoms are recognised as unique biological systems in which to study molecular evolution. Venom use has evolved numerous times among the insects, and insects today use venom to capture prey, defend themselves from predators, or to subdue and modulate host responses during parasitism. However, little is known ab...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/BST20190820

    authors: Walker AA

    更新日期:2020-08-28 00:00:00

  • Self-assembly in the carboxysome: a viral capsid-like protein shell in bacterial cells.

    abstract::Many proteins self-assemble to form large supramolecular complexes. Numerous examples of these structures have been characterized, ranging from spherical viruses to tubular protein assemblies. Some new kinds of supramolecular structures are just coming to light, while it is likely there are others that have not yet be...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章,评审

    doi:10.1042/BST0350508

    authors: Yeates TO,Tsai Y,Tanaka S,Sawaya MR,Kerfeld CA

    更新日期:2007-06-01 00:00:00

  • The methyl-CpG-binding protein MeCP2 and neurological disease.

    abstract::The methyl-CpG-binding protein MeCP2 was discovered over 15 years ago as part of a search for proteins that selectively bind methylated DNA. It is a nuclear protein that is largely chromatin-bound and has a strong preference for binding to methylated DNA sequences in vivo. Evidence from model systems shows that MeCP2 ...

    journal_title:Biochemical Society transactions

    pub_type:

    doi:10.1042/BST0360575

    authors: Bird A

    更新日期:2008-08-01 00:00:00

  • Plant copper chaperones.

    abstract::Copper chaperones, soluble copper-binding proteins, are essential for ensuring proper distribution of copper to cellular compartments and to proteins requiring copper prosthetic groups. They are found in all eukaryotic organisms. Orthologues of the three copper chaperones characterized in yeast, ATX1, CCS and COX17, a...

    journal_title:Biochemical Society transactions

    pub_type: 杂志文章

    doi:10.1042/bst0300732

    authors: Wintz H,Vulpe C

    更新日期:2002-08-01 00:00:00