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1.
Cutaneous wound healing is a complex and highly coordinated process where a number of different cell types participate to
renew the damaged tissue under the strict regulation of soluble and insoluble factors. One of the most versatile processes
involved in wound repair is proteolysis. During cell migration, proteins of extracellular matrix are cleaved, often creating
biologically active cleavage products, and proteolysis of cellular contacts leads to increased cell motility and division.
Moreover, proteases activate various growth factors and other proteases in wound and regulate growth factor signaling by shedding
growth factor receptors on cell surface. Normally, proteolysis is strictly controlled, and changes in protease activity are
associated with alterations in wound closure and scar formation. Here, we present the current view on the role of metalloproteinases
and the plasmin-plasminogen system in normal and aberrant cutaneous wound repair and discuss their role as potential therapeutic
targets for chronic ulcers or fibrotic scars.
Received 07 July 2008; received after revision 11 August 2008; accepted 13 August 2008 相似文献
2.
Sylvia E. Le Dévédec Kuan Yan Hans de Bont Veerander Ghotra Hoa Truong Erik H. Danen Fons Verbeek Bob van de Water 《Cellular and molecular life sciences : CMLS》2010,67(19):3219-3240
Cell migration is essential in a number of processes, including wound healing, angiogenesis and cancer metastasis. Especially,
invasion of cancer cells in the surrounding tissue is a crucial step that requires increased cell motility. Cell migration
is a well-orchestrated process that involves the continuous formation and disassembly of matrix adhesions. Those structural
anchor points interact with the extra-cellular matrix and also participate in adhesion-dependent signalling. Although these
processes are essential for cancer metastasis, little is known about the molecular mechanisms that regulate adhesion dynamics
during tumour cell migration. In this review, we provide an overview of recent advanced imaging strategies together with quantitative
image analysis that can be implemented to understand the dynamics of matrix adhesions and its molecular components in relation
to tumour cell migration. This dynamic cell imaging together with multiparametric image analysis will help in understanding
the molecular mechanisms that define cancer cell migration. 相似文献
3.
Chunzhang Yang Shervin Rahimpour Albert C. H. Yu Russell R. Lonser Zhengping Zhuang 《Cellular and molecular life sciences : CMLS》2013,70(22):4201-4211
Astrocytic activation is a cellular response to disturbances of the central nervous system (CNS). Recent advances in cellular and molecular biology have demonstrated the remarkable changes in molecular signaling, morphology, and metabolism that occur during astrocyte activation. Based on these studies, it has become clear that the astrocyte activation process is regulated by a variety of signaling pathways, which result in metabolic support, wound healing and scar formation. While normal astrocyte activation pathways drive homeostasis and/or repair in the CNS, dysregulation of these pathways can lead to astrocyte abnormalities, including glioma formation with similar phenotypes as reactive astrocytes. We review the principle pathways responsible for astrocytic activation, as well as their potential contribution to tumor formation in the CNS. 相似文献
4.
Hiroyuki Murota Yang Lingli Ichiro Katayama 《Cellular and molecular life sciences : CMLS》2017,74(23):4321-4328
Skin is an organ that is susceptible to damage by external injury, chronic inflammation, and autoimmunity. Tissue damage causes alterations in both the configuration and type of cells in lesional skin. This phenomenon, called tissue remodeling, is a universal biological response elicited by programmed cell death, inflammation, immune disorders, and tumorigenic, tumor proliferative, and cytoreductive activity. In this process, changes in the components of the extracellular matrix are required to provide an environment that facilitates tissue remodeling. Among these extracellular matrix components, periostin, a glycoprotein that is predominantly secreted from dermal fibroblasts, has attracted attention. Periostin localizes in the papillary dermis of normal skin, and is aberrantly expressed in the dermis of lesional skin in atopic dermatitis, scar, systemic/limited scleroderma, melanoma, cutaneous T cell lymphoma, and skin damage caused by allergic/autoimmune responses. Periostin induces processes that result in the development of dermal fibrosis, and activate or protract the immune response. The aim of this review was to summarize recent knowledge of the role of periostin in the pathogenesis of dermatoses, and to explore whether periostin is a potential therapeutic target for skin diseases. 相似文献
5.
Titz B Dietrich S Sadowski T Beck C Petersen A Sedlacek R 《Cellular and molecular life sciences : CMLS》2004,61(14):1826-1833
Matrix metalloproteinase 19 (MMP-19) is able to process various proteins of the basement membrane. To
investigate the impact of MMP-19 activity on endothelial cells in the context of tumor extracellular matrix (ECM),
we treated Matrigel matrix with an active recombinant MMP-19 and analyzed its effect on capillary-like formation.
Human microvascular endothelial cells (HMEC-1) could not form capillary-like formation on Matrigel treated with
recombinant MMP-19. Analyzing the Matrigel proteins, we found that MMP-19 preferentially cleaved nidogen-1. The
cleavage site of nidogen-1 was mapped to Thr867-Leu868. This cleavage separates the G3 globular domain containing
the binding site for the 1 chain of laminin-1 and collagen IV and thus abolishes the capacity of nidogen-1
to cross-link ECM proteins. Anti-nidogen antibodies directed against the G3 domain of nidogen-1 inhibited the
capillary-like structure formation to a similar extent as MMP-19. Since nidogen-1 is thought to stabilize
microvessels, MMP-19 might be one of the enzymes that interferes with stabilization or maturation of nascent
vasculature.Received 10 March 2004; received after revision 30 April 2004; accepted 26 May 2004 相似文献
6.
Werner E. G. Müller Maximilian Ackermann Shunfeng Wang Meik Neufurth Rafael Muñoz-Espí Qingling Feng Heinz C. Schröder Xiaohong Wang 《Cellular and molecular life sciences : CMLS》2018,75(1):21-32
In this study, the effect of inorganic polyphosphate (polyP) on the initial phase of angiogenesis and vascularization was investigated, applying the HUVEC cell tube formation assay. PolyP is a physiological and high energy phosphate polymer which has been proposed to act as a metabolic fuel in the extracellular space with only a comparably low ATP content. The experiments revealed that polyP accelerates tube formation of human umbilical vein endothelial cells (HUVEC), seeded onto a solidified basement membrane extract matrix which contains polyP-metabolizing alkaline phosphatase (ALP) activity. This effect is abolished by co-addition of apyrase, which degrades ATP to AMP and inorganic phosphate. The assumption that ATP, derived from polyP, activates HUVEC cells leading to tube formation was corroborated by experiments showing that addition of polyP to the cells causes a strong rise of ATP level in the culture medium. Finally, we show that at a later stage of cultivation of HUVEC cells, after 3 d, polyP causes a strong enhancement of the expression of the genes encoding for the two major matrix metalloproteinases (MMPs) released by endothelial cells during tube formation, MMP-9 and MMP-2. This stimulatory effect is again abrogated by addition of apyrase together with polyP. From these results, we propose that polyP is involved either directly or indirectly in energy supply, via ALP-mediated transfer of energy-rich phosphate under ATP formation. This ATP is utilized for the activation and oriented migration of endothelial cells and for the matrix organization during the initial phases of tube formation. 相似文献
7.
Thomae AW Baltin J Pich D Deutsch MJ Ravasz M Zeller K Gossen M Hammerschmidt W Schepers A 《Cellular and molecular life sciences : CMLS》2011,68(22):3741-3756
In eukaryotes, binding of the six-subunit origin recognition complex (ORC) to DNA provides an interactive platform for the
sequential assembly of pre-replicative complexes. This process licenses replication origins competent for the subsequent initiation
step. Here, we analyze the contribution of human Orc6, the smallest subunit of ORC, to DNA binding and pre-replicative complex
formation. We show that Orc6 not only interacts with Orc1–Orc5 but also with the initiation factor Cdc6. Biochemical and imaging
experiments reveal that this interaction is required for licensing DNA replication competent. Furthermore, we demonstrate
that Orc6 contributes to the interaction of ORC with the chaperone protein HMGA1a (high mobility group protein A1a). Binding
of human ORC to replication origins is not specified at the level of DNA sequence and the functional organization of origins
is poorly understood. We have identified HMGA1a as one factor that might direct ORC to AT-rich heterochromatic regions. The
systematic analysis of the interaction between ORC and HMGA1a revealed that Orc6 interacts with the acidic C-terminus of HMGA1a
and also with its AT-hooks. Both domains support autonomous replication if targeted to DNA templates. As such, Orc6 functions
at different stages of the replication initiation process. Orc6 can interact with ORC chaperone proteins such as HMGA1a to
facilitate chromatin binding of ORC and is also an essential factor for pre-RC formation. 相似文献
8.
Kirsten A. Bielefeld Saeid Amini-Nik Benjamin A. Alman 《Cellular and molecular life sciences : CMLS》2013,70(12):2059-2081
Following a skin injury, the damaged tissue is repaired through the coordinated biological actions that constitute the cutaneous healing response. In mammals, repaired skin is not identical to intact uninjured skin, however, and this disparity may be caused by differences in the mechanisms that regulate postnatal cutaneous wound repair compared to embryonic skin development. Improving our understanding of the molecular pathways that are involved in these processes is essential to generate new therapies for wound healing complications. Here we focus on the roles of several key developmental signaling pathways (Wnt/β-catenin, TGF-β, Hedgehog, Notch) in mammalian cutaneous wound repair, and compare this to their function in skin development. We discuss the varying responses to cutaneous injury across the taxa, ranging from complete regeneration to scar tissue formation. Finally, we outline how research into the role of developmental pathways during skin repair has contributed to current wound therapies, and holds potential for the development of more effective treatments. 相似文献
9.
H. Al-Kharobi R. El-Gendy D. A. Devine J. Beattie 《Cellular and molecular life sciences : CMLS》2014,71(8):1469-1476
The insulin-like growth factor (IGF) axis is a multicomponent molecular network which has important biological functions in the development and maintenance of differentiated tissue function(s). One of the most important functions of the IGF axis is the control of skeletal tissue metabolism by the finely tuned regulation of the process of osteogenesis. To achieve this, the IGF axis controls the activity of several cell types—osteoprogenitor cells, osteoblasts, osteocytes and osteoclasts to achieve the co-ordinated development of appropriate hard tissue structure and associated matrix deposition. In addition, there is an increasing awareness that the IGF axis also plays a role in the process of odontogenesis (tooth formation). In this review, we highlight some of the key findings in both of these areas. A further understanding of the role of the IGF axis in hard tissue biology may contribute to tissue regeneration strategies in cases of skeletal tissue trauma. 相似文献
10.
T cell memory is a crucial feature of the adaptive immune system in the defense against pathogens. During the last years,
numerous studies have focused their efforts on uncovering the signals, inflammatory cues, and extracellular factors that support
memory differentiation. This research is beginning to decipher the complex gene network that controls memory programming.
However, how the different signals, that a T cell receives during the process of differentiation, interplay to trigger memory
programming is still poorly defined. In this review, we focus on the most recent advances in the field and discuss how T cell
receptor signaling and inflammation control CD8 memory differentiation. 相似文献
11.
12.
Dudhia J 《Cellular and molecular life sciences : CMLS》2005,62(19-20):2241-2256
The primary function of articular cartilage to act as a self-renewing, low frictional material that can distribute load efficiently at joints is critically dependent upon the composition and organisation of the extracellular matrix. Aggrecan is a major component of the extracellular matrix, forming high molecular weight aggregates necessary for the hydration of cartilage and to meet its weight-bearing mechanical demands. Aggregate assembly is a highly ordered process requiring the formation of a ternary complex between aggrecan, link protein and hyaluronan. There is extensive age-associated heterogeneity in the structure and molecular stoichiometry of these components in adult human articular cartilage, resulting in diverse populations of complexes with a range of stabilities that have implications for cartilage mechanobiology and integrity. Recent findings have demonstrated that aggrecan can form ligands with other matrix proteins. These findings provide new insights into mechanisms for aggregate assembly and functional protein networks in different cartilage compartments with maturation and aging. 相似文献
13.
The efficient transport of blood and lymph relies on competent intraluminal valves that ensure unidirectional fluid flow through the vessels. In the lymphatic vessels, lack of luminal valves causes reflux of lymph and can lead to lymphedema, while dysfunction of venous valves is associated with venous hypertension, varicose veins, and thrombosis that can lead to edema and ulcerations. Despite their clinical importance, the mechanisms that regulate valve formation are poorly understood and have only recently begun to be characterized. Here, we discuss new findings regarding the development of venous and lymphatic valves that indicate the involvement of common molecular mechanisms in regulating valve formation in different vascular beds. 相似文献
14.
Harald W. Platta Stefanie Hagen Ralf Erdmann 《Cellular and molecular life sciences : CMLS》2013,70(8):1393-1411
Peroxisomes constitute a dynamic compartment of almost all eukaryotic cells. Depending on environmental changes and cellular demands peroxisomes can acquire diverse metabolic roles. The compartmentalization of peroxisomal matrix enzymes is a prerequisite to carry out their physiologic function. The matrix proteins are synthesized on free ribosomes in the cytosol and are ferried to the peroxisomal membrane by specific soluble receptors. Subsequent to cargo release into the peroxisomal matrix, the receptors are exported back to the cytosol to facilitate further rounds of matrix protein import. This dislocation step is accomplished by a remarkable machinery, which comprises enzymes required for the ubiquitination as well as the ATP-dependent extraction of the receptor from the membrane. Interestingly, receptor ubiquitination and dislocation are the only known energy-dependent steps in the peroxisomal matrix protein import process. The current view is that the export machinery of the receptors might function as molecular motor not only in the dislocation of the receptors but also in the import step of peroxisomal matrix protein by coupling ATP-dependent removal of the peroxisomal import receptor with cargo translocation into the organelle. In this review we will focus on the architecture and function of the peroxisomal receptor export machinery, the peroxisomal exportomer. 相似文献
15.
Tetraspanins regulate a variety of cellular functions. However, the general cellular mechanisms by which tetraspanins regulate these functions remain poorly understood. In this article we collected the observations that tetraspanins regulate the formation and/or development of various tubular structures of cell membrane. Because tetraspanins and their associated proteins (1) are localized at the tubular structures, such as the microvilli, adhesion zipper, foot processes, and penetration peg, and/or (2) regulate the morphogenesis of these membrane tubular structures, tetraspanins probably modulate various cellular functions through these membrane tubular structures. Some tetraspanins inhibit membrane tubule formation and/or extension, while others promote them. We predict that tetraspanins regulate the formation and/or development of various membrane tubular structures: (1) microvilli or nanovilli at the plasma membranes free of cell and matrix contacts, (2) membrane tubules at the plasma membrane of cell-matrix and cell-cell interfaces, and (3) membrane tubules at the intracellular membrane compartments. These different membrane tubular structures likely share a common morphogenetic mechanism that involves tetraspanins. Tetraspanins probably regulate the morphogenesis of membrane tubular structures by altering (1) the biophysical properties of the cell membrane such as curvature and/or (2) the membrane connections of cytoskeleton. Since membrane tubular structures are associated with cell functions such as adhesion, migration, and intercellular communication, in all of which tetraspanins are involved, the differential effects of tetraspanins on membrane tubular structures likely lead to the functional difference of tetraspanins. 相似文献
16.
J. Willems 《Cellular and molecular life sciences : CMLS》1961,17(8):344-345
Summary The macromolecules of high molecular polyamide films obtained in contact with (100) of KCl, KBr, and sucrose as a matrix are oriented by overgrowth in the form of a characteristic network of fibrils. This network formation of polyamides in contact with the atomic arrangement in crystal lattice planes as a matrix is proposed as a model for antibody formation. 相似文献
17.
18.
Megan L. H. Rose Maxwell T. Hincke 《Cellular and molecular life sciences : CMLS》2009,66(16):2707-2719
In this article, we review the results of recent proteomic and genomic analyses of eggshell matrix proteins and draw attention
to the impact of these data on current understanding of eggshell formation and function. Eggshell-specific matrix proteins
from avian (ovocleidins and ovocalyxins) and non-avian (paleovaterin) shells are discussed. Two possible roles for eggshell-specific
matrix proteins have been proposed; both reflect the protective function of the eggshell in avian reproduction: regulation
of eggshell mineralization and antimicrobial defense. An emerging concept is the dual role (mineralization/antimicrobial protection)
that certain eggshell matrix proteins can play. 相似文献
19.
L. W. van Laake E. G. van Donselaar J. Monshouwer-Kloots C. Schreurs R. Passier B. M. Humbel P. A. Doevendans A. Sonnenberg A. J. Verkleij Christine L. Mummery 《Cellular and molecular life sciences : CMLS》2010,67(2):277-290
Transplantation of human embryonic stem cell-derived cardiomyocytes (hESC-CM) for cardiac regeneration is hampered by the
formation of fibrotic tissue around the grafts, preventing electrophysiological coupling. Investigating this process, we found
that: (1) beating hESC-CM in vitro are embedded in collagens, laminin and fibronectin, which they bind via appropriate integrins;
(2) after transplantation into the mouse heart, hESC-CM continue to secrete collagen IV, XVIII and fibronectin; (3) integrin
expression on hESC-CM largely matches the matrix type they encounter or secrete in vivo; (4) co-transplantation of hESC-derived
endothelial cells and/or cardiac progenitors with hESC-CM results in the formation of functional capillaries; and (5) transplanted
hESC-CM survive and mature in vivo for at least 24 weeks. These results form the basis of future developments aiming to reduce
the adverse fibrotic reaction that currently complicates cell-based therapies for cardiac disease, and to provide an additional
clue towards successful engraftment of cardiomyocytes by co-transplanting endothelial cells. 相似文献
20.
Fábio G. Teixeira Miguel M. Carvalho Nuno Sousa António J. Salgado 《Cellular and molecular life sciences : CMLS》2013,70(20):3871-3882
The low regeneration potential of the central nervous system (CNS) represents a challenge for the development of new therapeutic strategies. Mesenchymal stem cells (MSCs) have been proposed as a possible therapeutic tool for CNS disorders. In addition to their differentiation potential, it is well accepted nowadays that their beneficial actions can also be mediated by their secretome. Indeed, it was already demonstrated, both in vitro and in vivo, that MSCs are able to secrete a broad range of neuroregulatory factors that promote an increase in neurogenesis, inhibition of apoptosis and glial scar formation, immunomodulation, angiogenesis, neuronal and glial cell survival, as well as relevant neuroprotective actions on different pathophysiological contexts. Considering their protective action in lesioned sites, MSCs’ secretome might also improve the integration of local progenitor cells in neuroregeneration processes, opening a door for their future use as therapeutical strategies in human clinical trials. Thus, in this review we analyze the current understanding of MSCs secretome as a new paradigm for the treatment of CNS neurodegenerative diseases. 相似文献