Fibrosis--a debilitating condition that can occur in most organs - is characterized by excess deposition of a collagen-rich extracellular matrix (ECM). At first sight, the activities of proteinases ...that can degrade matrix, such as matrix metalloproteinases (MMPs), might be expected to be under-expressed in fibrosis or, if present, could function to resolve the excess matrix. However, as we review here, some MMPs are indeed anti-fibrotic, whereas others can have pro-fibrotic functions. MMPs modulate a range of biological processes, especially processes related to immunity and tissue repair and/or remodeling. Although we do not yet know precisely how MMPs function during fibrosis--that is, the protein substrate or substrates that an individual MMP acts on to effect a specific process--experiments in mouse models demonstrate that MMP-dependent functions during fibrosis are not limited to effects on ECM turnover. Rather, data from diverse models indicate that these proteinases influence cellular activities as varied as proliferation and survival, gene expression, and multiple aspects of inflammation that, in turn, impact outcomes related to fibrosis.
Transition metal (oxy)hydroxides are promising electrocatalysts for the oxygen evolution reaction
. The properties of these materials evolve dynamically and heterogeneously
with applied voltage ...through ion insertion redox reactions, converting materials that are inactive under open circuit conditions into active electrocatalysts during operation
. The catalytic state is thus inherently far from equilibrium, which complicates its direct observation. Here, using a suite of correlative operando scanning probe and X-ray microscopy techniques, we establish a link between the oxygen evolution activity and the local operational chemical, physical and electronic nanoscale structure of single-crystalline β-Co(OH)
platelet particles. At pre-catalytic voltages, the particles swell to form an α-CoO
H
0.5H
O-like structure-produced through hydroxide intercalation-in which the oxidation state of cobalt is +2.5. Upon increasing the voltage to drive oxygen evolution, interlayer water and protons de-intercalate to form contracted β-CoOOH particles that contain Co
species. Although these transformations manifest heterogeneously through the bulk of the particles, the electrochemical current is primarily restricted to their edge facets. The observed Tafel behaviour is correlated with the local concentration of Co
at these reactive edge sites, demonstrating the link between bulk ion-insertion and surface catalytic activity.
Mechanisms of tendon injury and repair Thomopoulos, Stavros; Parks, William C.; Rifkin, Daniel B. ...
Journal of orthopaedic research,
June 2015, Letnik:
33, Številka:
6
Journal Article
Purpose of Review
Macrophages are central players in the immune response following tissue injury. These cells perform many functions, and the changing tissue microenvironment during injury shapes ...macrophage phenotype down a variety of polarized pathways. This review summarizes the current knowledge on the roles of macrophages during different stages of tissue injury, repair, and—if repair is not achieved—fibrosis.
Recent Findings
Macrophages present early in inflammation are functionally distinct from those at later stages. The predominant macrophage phenotype must transition from pro-inflammatory to pro-reparative to facilitate wound healing and scar resolution. If macrophages fail to acquire a tissue-healing phenotype, dysregulated signals can be drivers of disease processes, such as sustained, exuberant inflammation—as occurs in arthropathies—and fibrosis.
Summary
Comprehensive understanding of the roles of specific macrophage populations at different stages of the repair process will support the development of immune-targeted therapies for diseases such as fibrosis.
Repair following injury involves a range of processes – such as re-epithelialization, scar formation, angiogenesis, inflammation, and more – that function, often together, to restore tissue ...architecture. MMPs carry out diverse roles in all of these activities. In this article, we discuss how specific MMPs act on ECM during two critical repair processes: re-epithelialization and resolution of scar tissue. For wound closure, we discuss how two MMPs – MMP1 in human epidermis and MMP7 in mucosal epithelia – facilitate re-epithelialization by cleaving different ECM or ECM-associated proteins to affect similar integrin:matrix adhesion. In scars and fibrotic tissues, we discuss that a variety of MMPs carry out a diverse range of activities that can either promote or limit ECM deposition. However, few of these MMP-driven activities have been demonstrated to be due a direct action on ECM.
•We discuss how specific MMPs act on ECM during two critical repair processes: re-epithelialization and resolution of scar tissue.•For re-epithelialization, we discuss how MMP1 in skin and MMP7 in mucosal epithelia facilitate wound closure by cleaving different ECM or ECM-associated proteins to lessen integrin:matrix adhesion.•For scars and fibrotic tissues, we discuss that a variety of MMPs carry out a diverse range of activities that can either promote or limit ECM deposition.•However, few of these MMP-driven activities have been demonstrated to be due to a direct action on ECM.
Lithium-rich layered transition metal oxide positive electrodes offer access to anion redox at high potentials, thereby promising high energy densities for lithium-ion batteries. However, anion redox ...is also associated with several unfavorable electrochemical properties, such as open-circuit voltage hysteresis. Here we reveal that in Li
Ni
Co
Mn
O
, these properties arise from a strong coupling between anion redox and cation migration. We combine various X-ray spectroscopic, microscopic, and structural probes to show that partially reversible transition metal migration decreases the potential of the bulk oxygen redox couple by > 1 V, leading to a reordering in the anionic and cationic redox potentials during cycling. First principles calculations show that this is due to the drastic change in the local oxygen coordination environments associated with the transition metal migration. We propose that this mechanism is involved in stabilizing the oxygen redox couple, which we observe spectroscopically to persist for 500 charge/discharge cycles.
Biofilms—communities of bacteria encased in a polymer-rich matrix—confer bacteria with the ability to persist in pathologic host contexts, such as the cystic fibrosis (CF) airways. How bacteria ...assemble polymers into biofilms is largely unknown. We find that the extracellular matrix produced by Pseudomonas aeruginosa self-assembles into a liquid crystal through entropic interactions between polymers and filamentous Pf bacteriophages, which are long, negatively charged filaments. This liquid crystalline structure enhances biofilm function by increasing adhesion and tolerance to desiccation and antibiotics. Pf bacteriophages are prevalent among P. aeruginosa clinical isolates and were detected in CF sputum. The addition of Pf bacteriophage to sputum polymers or serum was sufficient to drive their rapid assembly into viscous liquid crystals. Fd, a related bacteriophage of Escherichia coli, has similar biofilm-building capabilities. Targeting filamentous bacteriophage or the liquid crystalline organization of the biofilm matrix may represent antibacterial strategies.
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•Filamentous Pf bacteriophage are produced by Pseudomonas aeruginosa•Pf phage interact with host and microbial polymers to assemble higher order structures•Pf phage increase the viscosity of polymers in cystic fibrosis airway secretions•The Pf-induced liquid crystal biofilm matrix boosts tolerance to desiccation and antibiotics
Filamentous Pf bacteriophage are often highly transcribed in P. aeruginosa biofilms. Secor et al. demonstrate that filamentous Pf bacteriophage interact with host and microbial polymers to assemble higher order liquid crystal structures. The organization of the biofilm matrix into a liquid crystal enhances biofilm adhesion, desiccation survival, and antibiotic tolerance.
As their name implies, MMPs were first described as proteases that degrade extracellular matrix proteins, such as collagens, elastin, proteoglycans, and laminins. However, studies of MMP function
in ...vivo have revealed that these proteinases act on a variety of extracellular protein substrates, often to activate latent forms of effector proteins, such as antimicrobial peptides and cytokines, or to alter protein function, such as shedding of cell-surface proteins. Because their substrates are diverse, MMPs are involved in variety of homeostatic functions, such as bone remodeling, wound healing, and several aspects of immunity. However, MMPs are also involved in a number of pathological processes, such as tumor progression, fibrosis, chronic inflammation, tissue destruction, and more. A key step in regulating MMP proteolysis is the conversion of the zymogen into an active proteinase. Several proMMPs are activated in the secretion pathway by furin proprotein convertases, but for most the activation mechanisms are largely not known. In this review, we discuss both authentic and potential mechanisms of proMMP activation.
This issue of Matrix Biology is devoted to exploring how metalloproteinases – here inclusive of related families of extracellular proteinases – act on extracellular matrix (ECM) proteins to influence ...an astonishing diversity of biological systems and diseases. Since their discovery in the 1960's, matrix metalloproteinases (MMPs) have oft and widely been considered as the principal mediators of ECM destruction. However, as becomes clear from several articles in this issue, MMPs affect processes that both promote and limit ECM assembly, structure, and quantity. Furthermore, it has become increasingly apparent that ECM proteolysis is neither the exclusive function of MMPs nor their only sphere of influence. Thus, other enzymes may be important participants in ECM proteolysis, and indeed they are. The ADAMTS (a disintegrin-like and metalloproteinase domain with thrombospondin type 1 repeat) proteinases, BMP/tolloid proteases, and meprins have all emerged as major mechanisms of ECM proteolysis. An aggregate view of proteolysis as an exquisitely specific and crucial post-translational modification of secreted proteins emerges from these reviews. The cumulative evidence strongly suggests that although some MMPs can and do cleave ECM components, notably fibrillar collagens, the majority of these proteinases are not key physiological participants in morphogenesis nor in control of matrix metabolism in homeostasis or disease. In contrast, deficiency of ADAMTS proteases leads to a remarkable array of morphogenetic defects and connective tissue disorders consistent with a specialized role in turnover of the embryonic provisional ECM and in ECM assembly. Astacin-related proteases emerge into crucial positions in ECM assembly and turnover, although they also have numerous roles related to morphogen and growth factor regulation. To further turn the traditional view on its head, it is clear that many MMPs are key participants in many, diverse immune and inflammation processes rather than ECM proteolysis. The overlap in the activities within and between these families leads to the view that ECM proteolysis, which is indispensable for life, was over-engineered to an extraordinary extent during vertebrate evolution. That these proteinases, which likely evolved within networks regulating morphogenesis, immunity and regeneration, also participate in diseases is a side effect of human longevity. Attempts to inhibit metalloproteinases in human diseases thus require continuing appraisal of their biological roles and cautious evaluation of potential new therapeutic opportunities.
Wound healing is a dynamic process that involves a coordinated response of many cell types representing distinct tissue compartments and is fundamentally similar among tissue types. Among the many ...gene products that are essential for restoration of normal tissue architecture, several members of the matrix metalloproteinase (MMP) family function as positive and, at times, negative regulators of repair processes. MMPs were initially thought to only function in the resolution phase of wound healing, particularly during scar resorption; however, recent evidence suggests that they also influence other wound-healing responses, such as inflammation and re-epithelialization. In this review, we discuss what is currently known about the function of MMPs in wound healing and will provide suggestions for future research directions.
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