tissue homeostasis (Total 1373616 Papers Found)

The distribution of the astrocytic gap junctional protein, connexin43 (Cx43) was compared immunohistochemically with that of amyloid plaques in Alzheimer's Disease (AD) brain. By light microscopy, cortical areas containing numerous beta/A4 amyloid plaques exhibited increased immunostaining density for Cx43 and some plaques corresponded exactly to sites of intensified Cx43 immunoreactivity. By electron microscopy, Cx43 was localized to astrocytic gap junctions in AD brain. Increased Cx43 expressi ...
The Hippo signaling pathway has been identified to be involved in development and tissue homeostasis during the past decade, and is evolutionarily conserved from Drosophila to mammals. It transduces the signal through a series of protein-protein interaction and kinase cascades, to control the cell number and organ size by inhibiting cell proliferation and promoting apoptosis. Dysregulation of the Hippo signaling pathway is associated with tumorigenesis and cancers, so it is a crucial target for ...
The Notch signaling pathway is essential for embryonic development, organogenesis, and tissue homeostasis. Aberrant Notch signaling is associated with several types of cancers. The active form of Notch receptor is its intracellular domain (NICD), which is released from the cell membrane by serial proteolytic cleavages following ligand binding. Dose-dependent effects of NICD on cellular phenotypes have been observed under several conditions although the underlying mechanisms have not been well st ...
Over the past years, several studies have been dedicated to understanding the physiological ability of the vent mussel Bathymodiolus azoricus to overcome the high metal concentrations present in their surrounding hydrothermal environment. Potential deep-sea mining activities at Azores Triple junction hydrothermal vent deposits would inevitably lead to the emergence of new fluid sources close to mussel beds, with consequent emission of high metal concentrations and potential resolubilization of C ...
Aging is characterized by the general decline in tissue and body function and the increased susceptibility to age-related pathologies, such as cancer. To maintain optimal tissue and body function, organisms have developed complex mechanisms for tissue homeostasis. Importantly, it is becoming apparent that these same mechanisms when deregulated also result in the development of age-related disease. The build in fail safe mechanisms of homeostasis, which prevent skewing toward disease, themselves ...
The cerebral palsy is highly actual issue of pediatrics, causing significant neurological disability. Though the great progress in the neuroscience has been recently achieved, the pathogenesis of cerebral palsy is still poorly understood. In this work, we reviewed available experimental and clinical data concerning the role of immune cells in pathogenesis of cerebral palsy. Maintaining of homeostasis in nervous tissue and its transformation in case of periventricular leukomalacia were analyzed. ...
The dioxin receptor (AhR) is possibly the best characterized xenobiotic receptor because of its essential role in mediating the harmful effects of highly toxic environmental pollutants. Despite the fact that AhR-dependent toxicity is a major environmental concern, compelling evidence has recently been produced unveiling novel and remarkable endogenous functions of AhR in cell physiology and tissue homeostasis. Adding to its role in cell proliferation and differentiation, AhR is also involved in ...
Inflammation is a highly coordinated host response to infection, injury, or cell stress. In most instances, the inflammatory response is pro-survival and is aimed at restoring physiological tissue homeostasis and eliminating invading pathogens, although exuberant inflammation can lead to tissue damage and death. Intravascular injection of adenovirus (Ad) results in virus accumulation in resident tissue macrophages that trigger activation of CXCL1 and CXCL2 chemokines via the IL-1α-IL-1RI signal ...
Apoptosis plays an important role in many developmental processes and contributes to cell and tissue homeostasis. Induction of apoptosis can involve the "intrinsic pathway", which is activated by diverse stress signals, and the "extrinsic pathway", which is activated by proapoptotic receptor signals at the cell surface. Excessive or aberrant apoptosis is a crucial factor in many human disorders, including polycystic kidney disease (PKD). Renal cyst formation is caused by dysregulation of cell pr ...
PURPOSE This review addressed the structural changes observed in salivary glands and pathogenic mechanisms resulting from oxidative stress caused by radiotherapy. The preventive and regenerative therapies for altered acinar morphology and glandular function were also reviewed. Among acute and late microscopic alterations in glandular tissue, there are particularly changes indicative of cell death, hypovascularization, formation of fibrous tissue and edema. A critical role was identified for the ...
Mucins are heavily O-glycosylated proteins primarily produced by glandular and ductal epithelial cells, either in membrane-tethered or secretory forms, for providing lubrication and protection from various exogenous and endogenous insults. However, recent studies have linked their aberrant overexpression with infection, inflammation, and cancer that underscores their importance in tissue homeostasis. In this review, we present current status of the existing mouse models that have been developed ...
NOTCH is a fundamental signaling system that regulates normal embryonic development and tissue homeostasis in adult life. NOTCH receptor is a single-pass transmembrane protein normally triggered via direct cell-to-cell contact, in which NOTCH ligands bind the extracellular domain of the receptor, inducing γ-secretase cleavage and release of intracellular domain. The intracellular domain binds to the transcriptional effector RBPJκ to activate transcription of target genes that regulate cell dif ...
Wnt-, Hedgehog- and Notch-signaling cascades are morphogen pathways that play crucial roles in development and tissue homeostasis. While morphogen pathways are tightly regulated at multiple levels, inappropriate activation of Wnt, Hedgehog and Notch signaling has been implicated into the pathogenesis of various diseases. In particular, Wnt, Hedgehog and Notch signaling have emerged as central players in the pathogenesis of fibrotic diseases. Here, we will review the pro-fibrotic effects of Wnt, ...
Important and novel roles for neuropeptide Y (NPY) signaling in the control of bone homeostasis have recently been identified, with deletion of either the Y1 or Y2 receptors resulting in a generalized increase in bone formation. Whereas the Y2 receptor-mediated anabolic response is mediated by a hypothalamic relay, the Y1-mediated response is likely mediated by osteoblastic Y1 receptors. The presence of Y1 receptors on osteoblasts and various other peripheral tissues suggests that, in addition t ...
PTK7 (protein tyrosine kinase 7) is an evolutionarily conserved transmembrane receptor regulating various processes in embryonic development and tissue homeostasis. On a cellular level PTK7 affects the establishment of cell polarity, the regulation of cell movement and migration as well as cell invasion. The PTK7 receptor has been shown to interact with ligands, co-receptors, and intracellular transducers of Wnt signaling pathways, pointing to a function in the fine-tuning of the Wnt signaling n ...
Heart failure is a major health problem. Accordingly, its pathophysiologic basis and pathogenic origins have received considerable research interest. To date much attention has focused on the importance of cardiac myocyte dysfunction and the adaptations of this muscular compartment as root causes of heart failure. Equally compelling to its origins, albeit less well recognized and understudied, is a role for the cardiac interstitium and its extracellular matrix. This dynamic compartment includes ...
How adult stem cell populations are recruited for tissue renewal and repair is a fundamental question of biology. Mobilization of stem cells out of their niches followed by correct migration and differentiation at a site of tissue turnover or injury are important requirements for proper tissue maintenance and regeneration. However, we understand little about the mechanisms that control this process, possibly because the best studied vertebrate adult stem cell systems are not readily amenable to ...
The Notch receptors have attracted considerable attention for their ability to control cellular functions that regulate embryo development and tissue homeostasis. Notch receptors act by controlling the expression of a specific set of target genes. If Notch signaling system can be so simple, and yet so complex in its pleiotropic effects, then a sophisticated network of regulatory mechanisms is required to maintain the control over the initiation, activity and termination of this signaling pathway ...
During dermal wound repair, hypoxia-driven proliferation results in dense but highly permeable, disorganized microvascular networks, similar to those in solid tumors. Concurrently, activated dermal fibroblasts generate an angiopermissive, provisional extracellular matrix (ECM). Unlike cancers, wounds naturally resolve via blood vessel regression and ECM maturation, which are essential for reestablishing tissue homeostasis. Mechanisms guiding wound resolution are poorly understood; one candidate ...
The connexins constitute a family of integral membrane proteins that form intercellular channels, enabling adjacent cells to directly exchange ions and small molecules. The connexin channels assemble into distinct plasma membrane domains known as gap junctions. Intercellular communication via gap junctions has an important role in regulating cell growth and differentiation, as well as in maintaining tissue homeostasis. Connexin43 (Cx43), the most ubiquitously expressed connexin isoform in human ...
Chronobiology is a field of biology that examines the generation of biological rhythms in various creatures and in many parts of body, and their adaptive fitness to solar- and lunar-related periodic phenomena. The synchronization of internal circadian clocks with external timing signals confers accurate phase response and tissue homeostasis. Herein we state a series of studies on circadian rhythms and introduce the brief history of chronobiology. We also present a detailed timeline of the discov ...
Extracellular proteolysis mediates tissue homeostasis. In cancer, altered proteolysis leads to unregulated tumor growth, tissue remodeling, inflammation, tissue invasion, and metastasis. The matrix metalloproteinases (MMPs) represent the most prominent family of proteinases associated with tumorigenesis. Recent technological developments have markedly advanced our understanding of MMPs as modulators of the tumor microenvironment. In addition to their role in extracellular matrix turnover and can ...
Apoptosis is an important mechanism for maintaining tissue homeostasis. The efficient induction and execution of apoptosis are essential for cell clearance in specific developmental situations. Insulin-like growth factor (IGF)-I is a survival factor for epithelial cells in the mammary gland, and its withdrawal or inhibition leads to apoptosis. In this paper we describe a novel mechanism that may lead to suppression of an IGF-I-mediated signaling pathway through cleavage of insulin receptor subst ...
The Notch pathway is an evolutionarily conserved signaling system that plays a critical pleiotropic role in regulating stem cell self-renewal and differentiation. The functional outcome of Notch signaling is highly dependent on cellular context and signal dosage. For example, distinct levels of Notch activity can either promote or suppress proliferation of mammary gland epithelial cells. In addition, Notch activation increases the self-renewal capacity of hematopoietic, neural and muscle stem ce ...
BACKGROUND/AIMS As conditional knockout mice for stat3 are impaired in liver regeneration after partial hepatectomy while those for gp130 have defects in early STAT3 phosphorylation but have normal DNA synthesis, late STAT3 phosphorylation induced independently of gp130 seems to be essential for liver regeneration. Since HGF and EGF can activate STAT3 via gp130-independent MET and EGFR, respectively, we assumed that these factors account for STAT3-dependent liver regeneration. Here, we investiga ...
In response to persistent DNA damage, induction into cell senescence promotes an immunogenic program which facilitates immune clearance of these damaged cells. Under physiological conditions, senescent cells can activate both innate and adaptive immune responses, functioning to maintain tissue homeostasis. In addition, emerging findings suggest that programmed induction of cell senescence may be important for regulating reproductive processes, partly facilitated by immune clearance. However, lik ...
Defense against bacterial infections requires activation of the immune response as well as timely reestablishment of tissue and immune homeostasis. Instauration of homeostasis is critical for tissue regeneration, wound healing, and host recovery. Recent studies revealed that severe infectious diseases frequently result from failures in homeostatic processes rather than from inefficient pathogen eradication. Type I interferons (IFN) appear to play a key role in such processes. Remarkably, the inv ...
Mitochondria-mediated apoptosis plays a central role in animal development and tissue homeostasis, and its alteration results in a range of malignant disorders including cancer. Upon apoptotic stimuli, the mitochondrial proteins cytochrome c and Smac/DIABLO are released into the cytosol, where they synergistically activate caspases by activating Apaf-1 and relieving the apoptotic inhibition by IAPs. Recent biochemical and structural studies reveal a molecular basis for these important events and ...
In this review, we have highlighted work that has clearly demonstrated that mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), a negative regulator of MAPKs, is an important signaling mediator in bone, muscle, and fat tissue homeostasis and differentiation. Further, we examined recent studies with particular focus on MKP-1 overexpression or deletion and its impact on tissues connected to bone. We also summarized regulation of MKP-1 by known skeletal regulators like parathyroid hormon ...
Modulation of gap junction structures and gap junctional communication is important in maintaining tissue homeostasis and can be controlled via phosphorylation of connexin 43 (Cx43) through several different signaling pathways. Transformation of cells by v-src has been shown to down-regulate gap junction communication coincident with an increase in tyrosine phosphorylation on Cx43. Activation of mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) also lead to down-regulation via p ...
Physiological cell turnover plays an important role in maintaining normal tissue function and architecture. This is achieved by the dynamic balance of cellular regeneration and elimination, occurring periodically in tissues such as the uterus and mammary gland, or at constant rates in tissues such as the gastrointestinal tract and adipose tissue. Apoptosis has been identified as the prevalent mode of physiological cell loss in most tissues. Cell turnover is precisely regulated by the interplay o ...
Caspase-8 or cellular FLICE-like inhibitor protein (cFLIP) deficiency leads to embryonic lethality in mice due to defects in endothelial tissues. Caspase-8(-/-) and receptor-interacting protein kinase-3 (RIPK3)(-/-), but not cFLIP(-/-) and RIPK3(-/-), double-knockout animals develop normally, indicating that caspase-8 antagonizes the lethal effects of RIPK3 during development. Here, we show that the acute deletion of caspase-8 in the gut of adult mice induces enterocyte death, disruption of tiss ...
Extracellular matrix (ECM) is an essential component of the stromal microenvironment both from a structural and a functional point of view. The ECM functions as a scaffold for tissue organization and regulates growth factors and chemokines availability thus contributing to maintain tissue homeostasis. Attachment of cells to ECM is essential to support cell survival, growth, and proliferation, and the lack of these interactions can trigger a type of cell death named anoikis. Several studies point ...
OBJECTIVE Review the role and therapeutic potential of peroxisome proliferator-activated receptor (PPAR) gamma in colonic disorders. DATA SOURCES Recent peer-reviewed scientific literature focusing on PPAR gamma in the colon. STUDY SELECTION Research reports using animal models, cultured cell lines, and clinical material were examined for content related to the role of PPAR gamma in normal colon cell function, colon cancer, and inflammatory bowel disease. Issues concerned with potential ther ...
Normal endometrial function requires a balance of progesterone (P4) and estrogen (E2) effects. An imbalance caused by increased E2 action and/or decreased P4 action can result in abnormal endometrial proliferation and, ultimately, endometrial adenocarcinoma, the fourth most common cancer in women. We have identified mitogen-inducible gene 6 (Mig-6) as a downstream target of progesterone receptor (PR) and steroid receptor coactivator (SRC-1) action in the uterus. Here, we demonstrate that absence ...
OBJECTIVE Insulin-like growth factor-1 (IGF1) regulates differentiation and growth of tissues and reduces stress and injury. IGF1 also in a tissue-specific manner modulates the differentiation and lipid storage capacity of adipocytes in vitro, but its roles in adipose tissue development and response to stress are not known. METHODS To study IGF1 in vivo, the cellular sources of adipose tissue Igf1 expression were identified and mice were generated with targeted deletion in adipocytes and macro ...
To investigate the cooperativity of different cell adhesion molecules in maintaining the structural integrity of the epidermis, we have generated mice deficient for both a classical cadherin, P-cadherin, and a desmosomal cadherin, desmoglein 3. In epithelial cells, P-cadherin is localized to the adherens junction, whereas desmoglein 3 is found in desmosomes. Previous studies have shown that these two junctional complexes are important for keratinocyte cell-cell adhesion. Both P-cadherin and desm ...
Canonical Wnt signalling plays an important role in development, tissue homeostasis, and cancer. At the cellular level, canonical Wnt signalling acts by regulating cell fate, cell growth, and cell proliferation. With regard to proliferation, there is increasing evidence for a complex interaction between canonical Wnt signalling and the cell cycle. Mitogenic Wnt signalling regulates cell proliferation by promoting G1 phase. In mitosis, components of the Wnt signalling cascade function directly in ...
The adherens junction (AJ) comprises multi-protein complexes required for cell-cell adhesion in embryonic development and adult tissue homeostasis. Mutations in key proteins and mis-regulation of AJ adhesive properties can lead to pathologies such as cancer. In recent years, the zebrafish has become an excellent model organism to integrate cell biology in the context of a multicellular organization. The combination of classical genetic approaches with new tools for live imaging and biophysical a ...
PURPOSE Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a complication of antiresorptive therapy with nitrogen-containing bisphosphonates (BP). With various suggestions as to pathogenesis, the etiology of BRONJ is not sufficiently understood. Osteoclasts and their precursors, that is, macrophages, are the main target cells of BP. BP can repolarize regeneration- and healing-associated M2 macrophages towards the tissue destructive M1-type. The current study aims to elucidate differences ...
Microenvironmental acidosis is a common feature of inflammatory loci, in which clearance of apoptotic cells is necessary for the resolution of inflammation. Although it is known that a low pH environment affects immune function, its effect on apoptotic cell clearance by macrophages has not been fully investigated. Here, we show that treatment of macrophages with low pH medium resulted in increased expression of stabilin-1 out of several receptors, which are known to be involved in PS-dependent r ...
Motile cilia have long been known to play a role in processes such as cell locomotion and fluid movement whereas the functions of primary cilia have remained obscure until recent years. To date, ciliary dysfunction has been shown to be causally linked to a number of clinical manifestations that characterize the group of human disorders known as ciliopathies. This classification reflects a common or shared cellular basis and implies that it is possible to associate a series of different human con ...
The Hedgehog (Hh) pathway, an evolutionarily conserved key regulator of embryonic patterning and tissue homeostasis, controls its target genes by managing the processing and activities of the Gli/Ci transcription factors. Little is known about the nuclear co-factors the Gli/Ci proteins recruit, and how they mechanistically control Hh target genes. Here, we provide evidence for the involvement of Parafibromin/Hyx as a positive component in Hh signaling. We found that hyx RNAi impaired Hh pathway ...
Eph receptors and their membrane-bound ligands are intimately involved in the control of morphogenic processes during embryonic development and adult tissue homeostasis. By their ability to orchestrate cell migration, pattern formation and tissue integrity they are also prone to be involved in carcinogenic growth. In this review we concentrate on their involvement in the normal and carcinogenic development of the breast. In this context we summarize their multi-faceted functions as tumor suppres ...
Proapoptotic Bcl-2 family members of the Bcl-2 homology (BH)3-only subgroup are critical for the establishment and maintenance of tissue homeostasis and can mediate apoptotic cell death in response to developmental cues or exogenously induced forms of cell stress. On the basis of the biochemical experiments as well as genetic studies in mice, the BH3-only proteins Bad and Bmf have been implicated in different proapoptotic events such as those triggered by glucose- or trophic factor-deprivation, ...
Milk fat globule-epidermal growth factor 8 (MFG-E8) is a glycoprotein that is abundantly expressed in various tissues and has a pivotal role in the phagocytic clearance of apoptotic cells. However, MFG-E8 has also gained significant attention because of its wide range of functions in autoimmunity, inflammation and tissue homeostasis. More recently, MFG-E8 has been identified as a critical regulator of bone homeostasis, being expressed in both, osteoblasts and osteoclasts. In addition, it was sho ...
The Hippo pathway plays a critical role in organ size control, tissue homeostasis and tumor genesis through its key transcription regulator Yes-associated protein1 (YAP1), but the mechanism underlying its role in lung cancer is unclear. We hypothesized that YAP1 influences FGFR1 signaling to maintain cancer stem-like cell (CSC) properties in FGFR1-amplified lung cancer. In support of this, our data confirms that expression levels of YAP1 are positively associated with those of FGFR1 in clinical ...
Galectins, a family of beta-galactoside binding lectins, have recently emerged as novel regulators of tissue homeostasis. Galectin-7 is predominantly expressed in stratified epithelia, especially in epidermis. We report here the generation of galectin-7-deficient mice that are viable and do not display phenotypical abnormalities in skin structure or expression of epidermal markers. However, these mice show unique defects in the maintenance of epidermal homeostasis in response to environmental ch ...
Keratins comprise the type I and type II intermediate filament-forming proteins and occur primarily in epithelial cells. They are encoded by 54 evolutionarily conserved genes (28 type I, 26 type II) and regulated in a pairwise and tissue type-, differentiation-, and context-dependent manner. Keratins serve multiple homeostatic and stress-enhanced mechanical and nonmechanical functions in epithelia, including the maintenance of cellular integrity, regulation of cell growth and migration, and prot ...
The abundance of innate and adaptive immune cells that reside together with trillions of beneficial commensal microorganisms in the mammalian gastrointestinal tract requires barrier and regulatory mechanisms that conserve host–microbial interactions and tissue homeostasis. This homeostasis depends on the diverse functions of intestinal epithelial cells (IECs), which include the physical segregation of commensal bacteria and the integration of microbial signals. Hence, IECs are crucial mediator ...