AIM: To investigate their expression and activity in the rat ileum after exposure to ionizing radiation along with that of the cellular effectors and molecular mediators involved in the regulation of MMPs. METHODS: Rats were exposed to a single 10-Gy dose of X-rays delivered to the abdomen. A combination of ...

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that have a number of important physiological roles including remodelling of the extracellular matrix, facilitating cell migration, cleaving cytokines, and activating defensins. However, excess MMP activity may lead to tissue destruction. The biology of MMP and the role of these proteases ...

Chronic microbial infections are associated with fibrotic and inflammatory reactions known as granulomas showing similarities to wound-healing and tissue repair processes. We have previously mapped three leishmaniasis susceptibility loci, designated lmr1, -2, and -3, which exert their effect independently of T cell immune responses. Here, we show that the wound ...

The coordinate modulation of the cellular functions of cadherins and integrins plays an essential role in fundamental physiological and pathological processes, including morphogenesis, tissue differentiation and renewal, wound healing, immune surveillance, inflammatory response, tumour progression, and metastasis. However, the molecular mechanisms underlying the fine-balanced relationship between cadherin and integrin functions ...

Damage to any tissue triggers a cascade of events that leads to rapid repair of the wound - if the tissue is skin, then repair involves re-epithelialization, formation of granulation tissue and contraction of underlying wound connective tissues. This concerted effort by the wounded cell layers is accompanied by, and ...

Animal epithelia are lined with apical surface matrices, which protect against pathogens, dehydration and physical damage of the underlying cells. The proteins and polysaccharides that comprise these protective barriers vary greatly within the animal kingdom and have evolved in response to the biological needs of various organisms. Yet the genetic ...

Regulation of the matrix metalloproteinases (MMPs), the major mediators of extracellular matrix (ECM) degradation, is crucial to regulate ECM proteolysis, which is important in metastasis. This study examined the effects of 3 flavonoid-enriched fractions (a crude fraction, an anthocyanin-enriched fraction, and a proanthocyanidin-enriched fraction), which were prepared from lowbush blueberries ...

Matrix metalloproteinases (MMPs) are a family of calcium-dependent, zinc-containing endoproteinases capable of degrading the extracellular matrix and basement membrane. Many inflammatory stimuli, such as wound healing, ultraviolet, hyperosmolarity, and stress, can stimulate production of inflammatory cytokines and a variety of MMPs, including gelatinases, collagenases, and stromelysins. Pro-inflammatory cytokines and growth ...

The differentiation of fibroblasts to contractile myofibroblasts, which is characterized by de novo expression of alpha-smooth muscle actin (alpha-SMA), is crucial for wound healing and a hallmark of tissue scarring and fibrosis. These processes often follow inflammatory events, particularly in soft tissues such as skin, lung and liver. Although inflammatory ...

The mechanisms by which fetal membranes (FM) rupture during the birth process are unknown. We have recently reported that FM weaken, at least in part, because of a developmental process of extracellular matrix remodeling and apoptosis. We now hypothesize that cytokines that normally increase in amniotic fluid at term induce ...

Cutaneous wound healing is a complex process that leads to the formation of a permanent scar in adult skin. In contrast, early gestation fetal skin undergoes scarless repair. Normally, the repair process in the skin begins with an acute inflammatory response. However, one of the most important aspects of scarless ...

Wound repair in horse limbs is often complicated by exuberant granulation tissue, a condition characterized by excessive fibroplasia and scarring and that resembles hypertrophic scars and keloids in man. The aim of this study was to compare microvascular occlusion and apoptosis in wounds of the limb with those of the ...

There is ample evidence supporting the view that alterations in the balance between matrix deposition and matrix degradation brought about by changes in the respective activities of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) contribute significantly to cardiac dysfunction and disease. Here we show that TIMP-1 was ...

Traditional wisdom has considered fibroblasts as contributing to the structural integrity of tissues rather than playing a dynamic role in physiological or pathological processes. It is only recently that they have been recognized as comprising diverse populations of cells exhibiting complex patterns of biosynthetic activity. They represent determinants that react ...

Apoptosis, or programmed cell death, is a complex network of biochemical pathways for controlling such events in a cell. Apoptosis is essential, as its failure can lead to disease. Because apoptosis concerns the regulation of sequential events, including the removal of inflammatory cells and the evolution of granulation tissue into ...

Venous leg ulcers are common and cause considerable morbidity in the population. As healing may be slow or may never be achieved, ulcers create persistent and substantial demands on clinical resources. Great efforts have been made to accelerate tissue repair in chronic venous leg ulcers with limited success. This may ...

Strategies for the tissue-engineering of living cardiac valve replacements are limited by a lack of appropriate scaffold materials that both permit cell viability and actively contribute to the growth of functional tissues. Components of the extracellular matrix can localize and modify growth factor signals, and by doing so impart instructional ...

Plasminogen activator inhibitor-1 (PAI-1) regulates the proteolytic activity of urokinase-type plasminogen activator (uPA) and there is increasing evidence for a PAI-1 role in regulating cell migration/invasion by other mechanisms like vitronectin (VN) binding and lipoprotein-receptor related protein (LRP) binding. We examined the role of PAI-1 to interact with uPA, VN, ...

BACKGROUND: Electrothermally-assisted capsular shrinkage has been gaining increased acceptance in the treatment of shoulder instability. Its indication in ACL-deficient knees has been discussed recently. METHODS: We examined the influence of immobilization on cell homeostasis of healing collagenous tissue after radiofrequency energy was applied to the patellar tendon in 23 rabbits. ...

The cornea plays a major role in the refraction of light to the retina. Therefore, the integrity and transparency of the corneal epithelium are critical to vision. Following injury, a combination of rapid signal transduction events and long-term cell migration are essential for wound closure. We have demonstrated previously that ...

The suppressor of cytokine signaling (SOCS) family of proteins are intracellular mediators of cytokine signaling. These proteins are induced rapidly by cytokine stimulation and act in a classic negative-feedback loop to attenuate the cellular response to the cytokine signal. In this study, we present the cloning and initial characterization of ...

PURPOSE: Corneal alkali injury is highly caustic, and present clinical therapies are limited. The purpose of this study was to investigate the ability of thymosin-beta4 (Taubeta4) to promote healing in an alkali injury model and the mechanisms involved in that process. METHODS: Corneas of BALB/c mice were injured with NaOH, ...

Matrix metalloproteinases (MMPs) regulate numerous functions in normal and disease processes; thus, irreversibly blocking their activity is a key step in regulating MMP catalysis. We previously showed in vitro that oxidizing intermediates generated by phagocytes inactivate MMPs by modifying specific amino acids. To assess whether this mechanism operates in vivo, ...

Considerable correlative evidence suggests an important role for matrix metalloproteinases (MMPs) in menstruation, a process which occurs naturally in very few species. In this study, MMP expression was examined in a mouse model of endometrial breakdown and repair and the functional importance of MMPs determined. In the model, progesterone support ...

Immune cells not only destroy pathogens but might also cause collateral injuries to normal tissues. The surprisingly low incidence of post-inflammatory complications is explained here by a 'danger-sensing' physiological mechanism that ensures the tissue-protecting negative feedback inhibition of overactive immune cells. We focus here on immunoregulatory influences of 'non-immune' signaling ...

Collagen fibrils in the extracellular matrix allow connective tissues such as tendon, skin and bone to withstand tensile forces. The fibrils are indeterminate in length, insoluble and form elaborate three-dimensional arrays that extend over numerous cell lengths. Studies of the molecular basis of collagen fibrillogenesis have provided insight into the ...

Bone marrow stem cells (BMSCs) can differentiate into several cells that participate in the healing of meniscal wounds. To test this hypothesis, we examined the effects of injected BMSCs on the healing of meniscal wounds. Autologous BMSCs from eight adult dogs were injected into meniscal wounds (knee joints). After 12 ...

Remodeling of the extracellular matrix--regulated by the matrix metalloproteinases (MMPs) and their endogenous inhibitors--is an important component of disease progression in many chronic disease states. Unchecked MMP activity can result in significant tissue damage, facilitate disease progression and is associated with host responses to pathologic injury, such as angiogenesis. The ...

Malignant glioma invasion into the surrounding brain tissue is still a major problem for any therapeutical methods. Matrix metalloproteinases (MMPs) have been implicated as important factors in this pathological process. In this study, one of the non-steroidal anti-inflammatory drugs (NSAIDs) indomethacin was employed to investigate the effect of inhibition of ...

Wound healing impairment represents a particularly challenging clinical problem to which no efficacious treatment regimens currently exist. The factors ensuring appropriate intercellular communication during wound repair are not completely understood. Although protein-type mediators are well-established players in this process, emerging evidence from both animal and human studies indicates that nitric ...

The angiopoietins are a class of growth factors that activate the Tie2 receptor and play important roles in the regulation of angiogenesis. Proper regulation of angiogenesis is required for both embryonic vascular development and physiological processes in the adult such as wound healing and the female reproductive cycle, while aberrant ...

Jasmonic acid (JA) is a lipid-derived signal that regulates plant defense responses to biotic stress. Here, we report the characterization of a JA-deficient mutant of tomato (Lycopersicon esculentum) that lacks local and systemic expression of defensive proteinase inhibitors (PIs) in response to wounding. Map-based cloning studies demonstrated that this phenotype ...

Advances in wound care are of great importance in clinical injury management. In this respect, the nuclear receptor peroxisome proliferator-activated receptor (PPAR)beta/delta occupies a unique position at the intersection of diverse inflammatory or anti-inflammatory signals that influence wound repair. This study shows how changes in PPARbeta/delta expression have a profound ...

As you saw in the first part of this description of interleukins, normal orchestration of wound healing, the protective immune response and inflammation involves many cells that must effectively communicate with each other. The means of this communication is often soluble messengers (cytokine) and many of them bear the title ...

Arginase activity is expressed by macrophages in healing wounds and other sites of inflammation and has been shown to modulate the synthesis of nitric oxide, polyamines, and collagen. The role of CCAAT/enhancer-binding protein beta (C/EBPbeta) in the regulation of macrophage arginase by different agonists was investigated using C/EBPbeta-/- and +/+ ...

OBJECTIVES: To build on work in laryngology and oral biology that suggests utility in the assay of secretions collected from wound sites as a predictive instrument to determine which infants will likely develop subglottic stenosis following endotracheal intubation and to document and describe the wound-healing process. DESIGN: Prospective, randomized design. ...

The matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases that play a key role in both physiological and pathological tissue remodeling. Human fibroblast collagenase (MMP-1) was the first vertebrate collagenase purified as a protein and cloned as a cDNA, and is considered the prototype for all the interstitial collagenases. ...

Scleroderma is a fibrotic condition characterized by immunologic abnormalities, vascular injury and increased accumulation of matrix proteins in the skin. Although the aetiology of scleroderma is not fully elucidated, a growing body of evidence suggests that extracellular matrix overproduction by activated fibroblasts results from complex interactions among endothelial cells, lymphocytes, ...

The extracellular matrix accumulates biologically active advanced glycation endproducts such as carboxymethyl-lysine (CML). Alikhani et al. recently reported that CML-rich collagen, representing an artifically aged matrix protein, induces apoptosis in vivo and in fibroblasts. This observation may have profound implications for the biology of cell-matrix interactions during aging.

Chronic progressive disease (CPD) are the Western world's major cause of mortality (National Center for Health Statistics. Vol. 52. National vital 176 statistics reports. Deaths: final data for 2001; 2003, p. 3). Most chronic diseases present with symptoms and signs specific for the dysfunctional organ. Nonetheless, substantial commonalities are identifiable ...

A new therapeutic trial aimed at assisting tissue regeneration at a body defect in size too large for self-repair has recently begun. The objective is to substitute the biological functions of damaged and injured organs by taking advantage of cells. For successful tissue regeneration, it is absolutely indispensable not only ...

Communication between the central nervous and the immune system occurs through chemical messengers secreted by nerve cells, endocrine organs, or immune cells. Psychological stressors can disrupt these networks. We have previously observed that disruption of the neuroendocrine immune system adversely influences a broad range of physiological processes including wound healing. ...

Following injury, as part of the wound-healing process, cell proliferation occurs mostly to replace damaged cells and to reconstitute the tissue back to normal condition/function. In the spinal cord some of the dividing cells following injury interfere with the repair processes. This interference occurs at the later stages of wound ...

Many components of the vertebrate immune system have evolved with dual, interrelated functions of both protecting injured tissues from infection and providing for tissue maintenance and repair of injuries. The capacity for organ regeneration, prominent among invertebrates and certain phylogenically primitive vertebrates, is poorly developed in mammals. We have proposed ...

Thrombin, a serine protease that plays a pivotal role in blood coagulation, wound healing, and angiogenesis, has also been implicated in the mitogenesis of various cell types. Previously, we showed that thrombin and the thrombin receptor agonist peptide (TRAP-14; SFLLRNPNDKYEPF) for protease-activated receptor 1 (PAR1) induce vascular endothelial growth factor ...

Fms-like tyrosine kinase-3 ligand (Flt3L) is a hemopoietic cytokine that stimulates the production of dendritic cells. This study evaluated the ability of Flt3L-enhanced dendritic cell production to increase the resistance of mice to a burn wound infection with Pseudomonas aeruginosa, a common source of infections in burn patients that have ...

Extracellular matrix metalloproteinase inducer (EMMPRIN) was originally identified on the tumor cell surface as an inducer of matrix metalloproteinase (MMP) production in neighboring fibroblasts. Here we demonstrate a role for EMMPRIN in MMP induction during corneal wound healing. MMP and EMMPRIN expression was analyzed in normal and ulcerated human corneas, ...

Angiogenesis is the formation of new capillary blood vessels from preexisting vessels. It is involved in many normal and diseased conditions, as well as in the application of tissue-engineered products. There has been extensive effort made to develop strategies for controlling pathological angiogenesis and for promoting vascularization in biomedical engineering ...

Tissues maintain homeostasis by monitoring and responding to varied physical interactions between cells and their microenvironment. In situations where acute tissue damage occurs, such as wounding, pathogenic assault, or toxic exposure, regulatory circuits that monitor tissue homeostasis are rapidly engaged to initiate tissue repair by regulating cell polarity, proliferation and ...

The uterus undergoes dynamic tissue remodeling throughout each reproductive cycle, which is regulated in part by the matrix metalloproteinases (MMP) system. The MMP system is comprised of the proteolytic factors, the MMPs, and their tissue inhibitors (TIMPs), which act in concert to modulate extracellular matrix turnover and cell behaviors and ...