scholarly journals Heparanase: A Multitasking Protein Involved in Extracellular Matrix (ECM) Remodeling and Intracellular Events

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 236 ◽  
Author(s):  
Valentina Masola ◽  
Gloria Bellin ◽  
Giovanni Gambaro ◽  
Maurizio Onisto
Keyword(s):  
Extracellular Matrix ◽  
Enzymatic Activity ◽  
Current Knowledge ◽  
Transmembrane Proteins ◽  
Ecm Remodeling ◽  
Physiological Conditions ◽  
Pathological Conditions ◽  
Low Levels ◽  
And Diffusion

Heparanase (HPSE) has been defined as a multitasking protein that exhibits a peculiar enzymatic activity towards HS chains but which simultaneously performs other non-enzymatic functions. Through its enzymatic activity, HPSE catalyzes the cutting of the side chains of heparan sulfate (HS) proteoglycans, thus contributing to the remodeling of the extracellular matrix and of the basal membranes. Furthermore, thanks to this activity, HPSE also promotes the release and diffusion of various HS-linked molecules like growth factors, cytokines and enzymes. In addition to being an enzyme, HPSE has been shown to possess the ability to trigger different signaling pathways by interacting with transmembrane proteins. In normal tissue and in physiological conditions, HPSE exhibits only low levels of expression restricted only to keratinocytes, trophoblast, platelets and mast cells and leukocytes. On the contrary, in pathological conditions, such as in tumor progression and metastasis, inflammation and fibrosis, it is overexpressed. With this brief review, we intend to provide an update on the current knowledge about the different role of HPSE protein exerted by its enzymatic and non-enzymatic activity.

scholarly journals Heparanase: A Multitasking Protein Involved in Extarcellular Matrix (ECM) Remodeling and Cellular Signaling

2018 ◽  
Author(s):  
Valentina Masola ◽  
Gloria Bellin ◽  
Giovanni Gambaro ◽  
Maurizio Onisto
Keyword(s):  
Enzymatic Activity ◽  
Normal Tissue ◽  
Current Knowledge ◽  
Transmembrane Proteins ◽  
Ecm Remodeling ◽  
Physiological Conditions ◽  
Pathological Conditions ◽  
Low Levels ◽  
And Diffusion

Heparanase (HPSE) has been defined as a multitasking protein that exhibits a peculiar enzymatic activity towards HS chains but which simultaneously performs other non-enzymatic functions. Through its enzymatic activity, HPSE catalyzes the cutting of the side chains of heparan sulfate (HS) proteoglycans, thus contributing to the remodeling of the extracellular matrix and of the basal membranes. Furthermore, thanks to this activity, HPSE also promotes the release and diffusion of various HS-linked molecules as growth factors, cytokines and enzymes. In addition to being an enzyme HPSE has been shown to possess the ability to trigger different signaling pathways by interacting with transmembrane proteins. In normal tissue and in physiological conditions, HPSE exhibits only low levels of expression restricted only to keratinocytes, trophoblast, platelets and mast cells and leukocytes. On the contrary, in pathological conditions, such as in tumor progression and metastasis, inflammation and fibrosis, it is overexpressed. With this brief review, we intend to provide an update on current knowledge about the different role of HPSE protein exerted by its enzymatic and not-enzymatic activity.

scholarly journals Heparanase: A Multitasking Protein Involved in Extarcellular Matrix (ECM) Remodeling and Intracellular Events

2018 ◽  
Author(s):  
Valentina Masola ◽  
Gloria Bellin ◽  
Giovanni Gambaro ◽  
Maurizio Onisto
Keyword(s):  
Enzymatic Activity ◽  
Normal Tissue ◽  
Current Knowledge ◽  
Transmembrane Proteins ◽  
Ecm Remodeling ◽  
Physiological Conditions ◽  
Pathological Conditions ◽  
Low Levels ◽  
And Diffusion

Heparanase (HPSE) has been defined as a multitasking protein that exhibits a peculiar enzymatic activity towards HS chains but which simultaneously performs other non-enzymatic functions. Through its enzymatic activity, HPSE catalyzes the cutting of the side chains of heparan sulfate (HS) proteoglycans, thus contributing to the remodeling of the extracellular matrix and of the basal membranes. Furthermore, thanks to this activity, HPSE also promotes the release and diffusion of various HS-linked molecules as growth factors, cytokines and enzymes. In addition to being an enzyme HPSE has been shown to possess the ability to trigger different signaling pathways by interacting with transmembrane proteins. In normal tissue and in physiological conditions, HPSE exhibits only low levels of expression restricted only to keratinocytes, trophoblast, platelets and mast cells and leukocytes. On the contrary, in pathological conditions, such as in tumor progression and metastasis, inflammation and fibrosis, it is overexpressed. With this brief review, we intend to provide an update on current knowledge about the different role of HPSE protein exerted by its enzymatic and not-enzymatic activity.

Recent data concerning heparanase: focus on fibrosis, inflammation and cancer

2015 ◽  
Vol 6 (5-6) ◽  
pp. 415-421 ◽  
Author(s):  
Maria Francesca Secchi ◽  
Valentina Masola ◽  
Gianluigi Zaza ◽  
Antonio Lupo ◽  
Giovanni Gambaro ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Transmembrane Proteins ◽  
Basement Membranes ◽  
Attractive Potential ◽  
Clinical Settings ◽  
Nuclear Level ◽  
Physiological Conditions ◽  
Pathological Conditions ◽  
Conceptual Overview ◽  
And Diffusion

AbstractHeparanase (HPSE) is a multitasking protein characterized by enzymatic and non-enzymatic activities. By means of its enzymatic activity, HPSE catalyzes the cutting of the side chains of heparan sulfate (HS) proteoglycans, thereby inducing the remodeling of the extracellular matrix and basement membranes. Thanks to the cleavage of HS, HPSE also promotes the release and diffusion of several HS-linked molecules such as growth factors, cytokines and enzymes. In addition to degrading HS chains, HPSE has non-enzymatic functions that trigger several signaling pathways. This signaling activity is achieved by interacting with transmembrane proteins, activating kinases such as Akt and Src, or modulating the activity of factors such as FGF-2 and TGF-β. Several studies have recently highlighted a possible intracellular activity for HPSE, particularly at nuclear level. While HPSE activity is quite limited in physiological conditions, its demonstrated increasing involvement in various pathological conditions, such as in tumor progression and renal disease, have attracted the attention of a growing number of researchers. The fact that no other molecule is capable of performing the same function as HPSE makes this enzyme an attractive potential target of medical treatment. With this short conceptual overview, we aim to provide an update on current knowledge concerning the HPSE protein in the experimental and clinical settings, paying particular attention to its role in fibrosis, inflammation and cancer.

scholarly journals Matrix Metalloproteinases: A Review

1993 ◽  
Vol 4 (2) ◽  
pp. 197-250 ◽  
Author(s):  
H. Birkedal-Hansen ◽  
W.G.I. Moore ◽  
M.K. Bodden ◽  
L.J. Windsor ◽  
B. Birkedal-Hansen ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Current Knowledge ◽  
Periodontal Diseases ◽  
Present Review ◽  
Transcriptional Level ◽  
Substrate Specificities ◽  
Pathological Conditions ◽  
Final Segment ◽  
Extracellular Level

Matrix metalloproteinases (MMPs) are a family of nine or more highly homologous Zn++endopeptidases that collectively cleave most if not all of the constituents of the extracellular matrix. The present review discusses in detail the primary structures and the overlapping yet distinct substrate specificities of MMPs as well as the mode of activation of the unique MMP precursors. The regulation of MMP activity at the transcriptional level and at the extracellular level (precursor activation, inhibition of activated, mature enzymes) is also discussed. A final segment of the review details the current knowledge of the involvement of MMP in specific developmental or pathological conditions, including human periodontal diseases.

scholarly journals The Role of Changes in Extracellular Matrix of Cartilage in the Presence of Inflammation on the Pathology of Osteoarthritis

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Maricela Maldonado ◽  
Jin Nam
Keyword(s):  
Extracellular Matrix ◽  
Repair Process ◽  
Cellular Component ◽  
Ecm Remodeling ◽  
Multiple Factors ◽  
Inflammatory Conditions ◽  
Composition And Structure ◽  
Poor Understanding ◽  
Wear And Tear

Osteoarthritis (OA) is a degenerative disease that affects various tissues surrounding joints such as articular cartilage, subchondral bone, synovial membrane, and ligaments. No therapy is currently available to completely prevent the initiation or progression of the disease partly due to poor understanding of the mechanisms of the disease pathology. Cartilage is the main tissue afflicted by OA, and chondrocytes, the sole cellular component in the tissue, actively participate in the degeneration process. Multiple factors affect the development and progression of OA including inflammation that is sustained during the progression of the disease and alteration in biomechanical conditions due to wear and tear or trauma in cartilage. During the progression of OA, extracellular matrix (ECM) of cartilage is actively remodeled by chondrocytes under inflammatory conditions. This alteration of ECM, in turn, changes the biomechanical environment of chondrocytes, which further drives the progression of the disease in the presence of inflammation. The changes in ECM composition and structure also prevent participation of mesenchymal stem cells in the repair process by inhibiting their chondrogenic differentiation. This review focuses on how inflammation-induced ECM remodeling disturbs cellular activities to prevent self-regeneration of cartilage in the pathology of OA.

Role of extravascular protein in capillary-tissue fluid exchange

1978 ◽  
Vol 234 (1) ◽  
pp. H52-H58
Author(s):  
E. P. Salathe ◽  
R. Venkataraman
Keyword(s):  
Mathematical Model ◽  
Perturbation Theory ◽  
Osmotic Pressure ◽  
Analytic Solutions ◽  
Tissue Fluid ◽  
Fluid Exchange ◽  
Numerical Examples ◽  
Pathological Conditions ◽  
And Diffusion

A mathematical model of capillary-tissue fluid exchange is presented. The effect of variation in plasma and interstitial osmotic pressure that occurs as a result of convection and diffusion of protein is examined. Analytic solutions to the resulting equations are obtained by using the methods of perturbation theory. It is found that fluid exchange can significantly alter the pericapillary interstitial osmotic pressure, reducing both filtration and reabsorption. Variation in plasma osmotic pressure is important only for certain pathological conditions in which excessive filtration occurs. Specific numerical examples are presented which show quantitatively the extent of these effects for various normal and pathological conditions of physiological interest.

Renal interstitial hyaluronan: functional aspects during normal and pathological conditions

2012 ◽  
Vol 302 (11) ◽  
pp. R1235-R1249 ◽  
Author(s):  
Sara Stridh ◽  
Fredrik Palm ◽  
Peter Hansell
Keyword(s):  
Current Knowledge ◽  
Stone Formation ◽  
Ischemia Reperfusion ◽  
The Body ◽  
Receptor Expression ◽  
Whole Body ◽  
Hydration Status ◽  
Hyaluronan Synthases ◽  
Pathological Conditions

The glycosaminoglycan (GAG) hyaluronan (HA) is recognized as an important structural component of the extracellular matrix, but it also interacts with cells during embryonic development, wound healing, inflammation, and cancer; i.e., important features in normal and pathological conditions. The specific physicochemical properties of HA enable a unique hydration capacity, and in the last decade it was revealed that in the interstitium of the renal medulla, where the HA content is very high, it changes rapidly depending on the body hydration status while the HA content of the cortex remains unchanged at very low amounts. The kidney, which regulates fluid balance, uses HA dynamically for the regulation of whole body fluid homeostasis. Renomedullary HA elevation occurs in response to hydration and during dehydration the opposite occurs. The HA-induced alterations in the physicochemical characteristics of the interstitial space affects fluid flux; i.e., reabsorption. Antidiuretic hormone, nitric oxide, angiotensin II, and prostaglandins are classical hormones/compounds involved in renal fluid handling and are important regulators of HA turnover during variations in hydration status. One major producer of HA in the kidney is the renomedullary interstitial cell, which displays receptors and/or synthesis enzymes for the hormones mentioned above. During several kidney disease states, such as ischemia-reperfusion injury, tubulointerstitial inflammation, renal transplant rejection, diabetes, and kidney stone formation, HA is upregulated, which contributes to an abnormal phenotype. In these situations, cytokines and other growth factors are important stimulators. The immunosuppressant agent cyclosporine A is nephrotoxic and induces HA accumulation, which could be involved in graft rejection and edema formation. The use of hyaluronidase to reduce pathologically overexpressed levels of tissue HA is a potential therapeutic tool since diuretics are less efficient in removing water bound to HA in the interstitium. Although the majority of data describing the role of HA originate from animal and cell studies, the available data from humans demonstrate that an upregulation of HA also occurs in diabetic kidneys, in transplant-rejected kidneys, and during acute tubular necrosis. This review summarizes the current knowledge regarding interstitial HA in the role of regulating kidney function during normal and pathological conditions. It encompasses mechanistic insights into the background of the heterogeneous intrarenal distribution of HA; i.e., late nephrogenesis, its regulation during variations in hydration status, and its involvement during several pathological conditions. Changes in hyaluronan synthases, hyaluronidases, and binding receptor expression are discussed in parallel.

scholarly journals Tackling Chronic Pain and Inflammation through the Purinergic System

2018 ◽  
Vol 25 (32) ◽  
pp. 3830-3865 ◽  
Author(s):  
Giulia Magni ◽  
Daniele Riccio ◽  
Stefania Ceruti
Keyword(s):  
Membrane Transporters ◽  
Receptor Subtypes ◽  
Physiological Conditions ◽  
Purinergic System ◽  
Inflammatory Conditions ◽  
Pathological Conditions ◽  
Inflammatory Processes ◽  
Clear Identification ◽  
The Many

The purinergic system is composed of purine and pyrimidine transmitters, the enzymes that modulate the interconversion of nucleotides and nucleosides, the membrane transporters that control their extracellular concentrations, and the many receptor subtypes that are responsible for their cellular responses. The components of this system are ubiquitously localized in all tissues and organs, and their involvement in several physiological conditions has been clearly demonstrated. Moreover, extracellular purine and pyrimidine concentrations rise several folds under pathological conditions like tissue damage, ischemia, and inflammation, which suggest that this signaling system might contribute both to disease outcome and, possibly, to its tentative resolution. The complexity of this system has greatly impaired the clear identification of the mediators and receptors that are actually involved in a given pathology, also due to the often opposite roles played by the various receptor subtypes. Nevertheless, this knowledge is fundamental for the possible exploitation of these molecular entities as targets for the development of new pharmacological approaches. In this review, we aim at highlighting what is currently known on the role of the purinergic system in various pain conditions and during inflammatory processes. Although some confusion may arise from conflicting results, literature data clearly show that targeting specific purinergic receptors may represent an innovative approach to various pain and inflammatory conditions, and that new purine-based drugs are now very close to reach the market with these indications.

scholarly journals The Role of Extracellular Vesicles in the Progression of Tumors towards Metastasis

2021 ◽  
Author(s):  
Bhaskar Basu ◽  
Subhajit Karmakar
Keyword(s):  
Extracellular Matrix ◽  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Stromal Cells ◽  
Lipid Membrane ◽  
Recipient Cell ◽  
Ecm Remodeling ◽  
Secondary Tumor ◽  
Metastatic Cells

Extracellular vesicles (EVs) are cell-derived lipid membrane bound vesicles that serve as mediators of intercellular communication. EVs have been found to regulate a wide range of cellular processes through the transference of genetic, protein and lipid messages from the host cell to the recipient cell. Unsurprisingly, this major mode of intracellular communication would be abrogated in cancer. Ever increasing evidence points towards a key role of EVs in promoting tumor development and in contributing to the various stages of metastasis. Tumor released EVs have been shown to facilitate the transference of oncogenic proteins and nucleic acids to other tumor cells and to the surrounding stromal cells, thereby setting up a tumor permissive microenvironment. EVs released from tumor cells have been shown to promote extracellular matrix (ECM) remodeling through the modulation of neighboring tumor cells and stromal cells. EVs released from disseminated tumor cells have been reported to attract circulating tumor cells (CTCs) via chemotaxis and induce the production of specific extracellular matrix components from neighboring stromal cells so as to support the growth of metastatic cells at the secondary tumor site. Circulating levels of tumor derived EVs of patients have been correlated with incidence of metastasis and disease relapse.

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