scholarly journals The Role of Macrophages in Vascular Repair and Regeneration after Ischemic Injury

2020 ◽  
Vol 21 (17) ◽  
pp. 6328
Author(s):  
Huiling Hong ◽  
Xiao Yu Tian
Keyword(s):  
Tissue Injury ◽  
Direct Interaction ◽  
Cell Types ◽  
Short Review ◽  
Potential Interaction ◽  
Hindlimb Ischemia ◽  
Vascular Repair ◽  
Injury Repair ◽  
Vascular Beds

Macrophage is one of the important players in immune response which perform many different functions during tissue injury, repair, and regeneration. Studies using animal models of cardiovascular diseases have provided a clear picture describing the effect of macrophages and their phenotype during injury and regeneration of various vascular beds. Many data have been generated to demonstrate that macrophages secrete many important factors including cytokines and growth factors to regulate angiogenesis and arteriogenesis, acting directly or indirectly on the vascular cells. Different subsets of macrophages may participate at different stages of vascular repair. Recent findings also suggest a direct interaction between macrophages and other cell types during the generation and repair of vasculature. In this short review, we focused our discussion on how macrophages adapt to the surrounding microenvironment and their potential interaction with other cells, in the context of vascular repair supported by evidences mostly from studies using hindlimb ischemia as a model for studying post-ischemic vascular repair.

scholarly journals Hyaluronan as an Immune Regulator in Human Diseases

2011 ◽  
Vol 91 (1) ◽  
pp. 221-264 ◽  
Author(s):  
Dianhua Jiang ◽  
Jiurong Liang ◽  
Paul W. Noble
Keyword(s):  
Cell Surface ◽  
Tissue Injury ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Surface Proteins ◽  
Human Diseases ◽  
Inflammatory Genes ◽  
Extracellular Matrix Components ◽  
Injury And Repair

Accumulation and turnover of extracellular matrix components are the hallmarks of tissue injury. Fragmented hyaluronan stimulates the expression of inflammatory genes by a variety of immune cells at the injury site. Hyaluronan binds to a number of cell surface proteins on various cell types. Hyaluronan fragments signal through both Toll-like receptor (TLR) 4 and TLR2 as well as CD44 to stimulate inflammatory genes in inflammatory cells. Hyaluronan is also present on the cell surface of epithelial cells and provides protection against tissue damage from the environment by interacting with TLR2 and TLR4. Hyaluronan and hyaluronan-binding proteins regulate inflammation, tissue injury, and repair through regulating inflammatory cell recruitment, release of inflammatory cytokines, and cell migration. This review focuses on the role of hyaluronan as an immune regulator in human diseases.

The emerging role of NPNT in tissue injury repair and bone homeostasis

2017 ◽  
Vol 233 (3) ◽  
pp. 1887-1894 ◽  
Author(s):  
Youqiang Sun ◽  
Vincent Kuek ◽  
Heng Qiu ◽  
Jennifer Tickner ◽  
Leilei Chen ◽  
...  
Keyword(s):  
Tissue Injury ◽  
Bone Homeostasis ◽  
Injury Repair

Abstract 200: Novel Interaction of Spinophilin with Alpha1a-Adrenergic Receptor and its Genetic Variant in Cardiovascular Cells

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Ekaterina Babaeva ◽  
Irina Gradinaru ◽  
Debra A Schwinn ◽  
Anush Oganesian
Keyword(s):  
Genetic Variant ◽  
Direct Interaction ◽  
Cell Types ◽  
Intracellular Loop ◽  
Preliminary Results ◽  
Protein Levels ◽  
Cardiovascular Cells ◽  
Novel Target ◽  
G Protein Coupled

Activation of α 1 -Adrenergic Receptors (α 1 ARs), members of the G protein-coupled receptor (GPCR) superfamily, in response to stimulation of the sympathetic nervous system by catecholamines plays a major role in regulating cardiovascular (CV) function. Among three α 1 AR subtypes (α 1a ,α 1b ,α 1d ), α 1a ARs predominate in human resistant vessels and in heart. Recently, we discovered that naturally occurring human α 1a AR-G247R (247R) genetic variant, identified in the 3 rd intracellular loop (3iL) of the receptor in highly hypertensive patient, triggers constitutive hyperproliferation in CV cells (cardiomyoblasts, smooth muscle cells (SMC) and fibroblasts), which may lead to myocardial fibrosis and remodeling. In fibroblasts and cardiomyoblasts 247R triggered hyperproliferation is due to constitutive active coupling to Gq-independent βarrestin1/MMP/EGFR/ERK dependent pathway, while in SMC it is Gq- and MMP/EGFR/ERK-dependent. Here we report that α 1a AR-WT (WT) and 247R differentially interact with ubiquitous multi-domain scaffold protein spinophilin (SPL) that binds to 3iL of several GPCRs competing with arrestin thereby prolonging their signaling. The role of SPL in CV regulation is poorly studied. We hypothesized that SPL mediates constitutive signaling of 247R and examined whether SPL directly interacts with α 1a AR-WT or 247R. Our preliminary results reveal a direct interaction of SPL with WT and 247R: the SPL-WT interaction appears to be stronger as determined by co-immunoprecipitation. Different domains of SPL differentially interact with WT or 247R. SPL 1-480aa fragment interacts stronger with WT indicating interaction with 3iL, while SPL 480-817 fragment interacts stronger with 247R. Our preliminary results also demonstrate that 247R expression in all three cell types elevates endogenous SPL protein levels. Importantly, inhibition of SPL expression with specific siRNA reduces 247R-triggered hyperproliferation in SMC and cardiomyoblasts to near normal levels, while SPL knockdown has no effect in WT cells. Thus, we identified SPL as a novel protein involved in interacting and signaling of α 1a AR and its genetic variant in CV cells and that SPL could be considered as a potentially novel target in α 1a AR-mediated cardiovascular disorders.

Immune Mechanisms and Related Targets for the Treatment of Fibrosis in Various Organs

2022 ◽  
Vol 22 ◽  
Author(s):  
Anita A Pinar ◽  
Chrishan S S Samuel
Keyword(s):  
Tissue Injury ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Specific Cell ◽  
Fibrotic Response ◽  
Immune Mechanisms ◽  
Emerging Therapies ◽  
Fibrotic Process ◽  
Antigen Presenting

Abstract: Inflammation and fibrosis are two inter‐related disease pathologies with several overlapping components. Three specific cell types, macrophages, T helper cells and myofibroblasts, each play important roles in regulating both processes. Following tissue injury, an inflammatory stimulus is often necessary to initiate tissue repair, where cytokines released from infiltrating and resident immune and inflammatory cells stimulate the proliferation and activation of extracellular matrix-producing myofibroblasts. However, persistent tissue injury drives an inappropriate pro‐fibrotic response. Additionally, activated myofibroblasts can take on the role of traditional antigen-presenting cells, secrete pro‐inflammatory cytokines, and recruit inflammatory cells to fibrotic foci, amplifying the fibrotic response in a vicious cycle. Moreover, inflammatory cells have been shown to play contradictory roles in the initiation, amplification and resolution of fibrotic disease processes. The central role of the inflammasome molecular platform in contributing to fibrosis is only beginning to be fully appreciated. In this review, we discuss the immune mechanisms that can lead to fibrosis, the inflammasomes that have been implicated in the fibrotic process in the context of the immune response to injury, and also discuss current and emerging therapies that target inflammasome-induced collagen deposition to treat organ fibrosis.

CD47 Glycoprotein Interacts with p4.1R and p55 in the Erythrocyte.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1126-1126
Author(s):  
Neil D. Avent ◽  
Zoe E. Plummer ◽  
David J. Head
Keyword(s):  
Erythrocyte Membrane ◽  
Direct Interaction ◽  
Potential Interaction ◽  
Erythrocyte Membranes ◽  
Mature Erythrocyte ◽  
Diffuse Fraction ◽  
Cytoplasmic Face ◽  
Free Translation

Abstract CD47 is a 47–50kDa membrane glycoprotein with 5 known isoforms. The role of CD47 within the erythrocyte membrane remains the subject of much research and debate though we recently provided evidence that CD47 may function as an inducer of eryptosis (Head et al, 2005). As both a cytoskeletal linked fraction and a smaller membrane diffuse fraction of CD47 exists, it is most likely that there are a number of protein species that are able to bind to CD47 at its cytoplasmic face. Our research has focused on a study of the molecular interactions of erythrocyte CD47 with erythrocyte membrane skeletal proteins protein 4.1R (p4.1R), protein 4.2 (p4.2) and p55. Here we demonstrate the ubiquitous expression of all CD47 isoforms in haemopoietic cells and tissues using basic and real-time PCR. Via immunoprecipitation of CD47 from mature erythrocyte membranes using the anti-CD47 mAb BRIC-126, yeast two-hybrid analysis and in vitro co-immunoprecipitation of 35[S] labelled peptides in a cell-free translation procedure, a novel ternary complex involving CD47, p55 and p4.1R has been indicated. More specifically, the potential interaction between p55/p4.1R and the cytoplasmic face of CD47 has been localised to the PDZ and FERM domain of these proteins respectively. Though research suggests p4.2 provides the major cytoskeletal attachment of CD47 (Bruce et al, 2002; Mouro-Chanteloup et al, 2003), a direct interaction between CD47 and p4.2 was not suggested by our study and remains undemonstrated. We continue to further the evidence for a functional role of CD47 in eryptosis. We propose p4.1R links CD47 to the apoptotic machinery of the cell and suggest a mechanism whereby cytoskeletal rearrangement and PS exposure occurs. 4.1null cells have been obtained and are currently being investigated. Further characterisation of the eryptotic pathway may offer insight into potential therapies for erythroleukaemia characterised by resistance of the erythroid lineage to apoptosis. This work has equal significance in the stabilization of red cell preparations in the blood transfusion setting.

scholarly journals The role of pulmonary mesenchymal cells in airway epithelium regeneration during injury repair

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Suyun Fang ◽  
Suhong Zhang ◽  
Haiting Dai ◽  
Xiaoxiang Hu ◽  
Changgong Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Airway Epithelium ◽  
Cell Types ◽  
Mesenchymal Cells ◽  
Ciliated Cells ◽  
Epithelial Stem Cells ◽  
Injury Repair ◽  
Club Cells

Abstract Background The airways of mammalian lung are lined with highly specialized cell types that are the target of airborne toxicants and injury. Several epithelial cell types and bone marrow-derived mesenchymal stem cells have been identified to serve as stem cells during injury repair. However, the contributions of endogenous mesenchymal cells to recruitment, expansion or differentiation of stem cells, and repair and reestablishment of the normal composition of airway epithelium following injury have not been addressed. Methods The role of mouse pulmonary mesenchymal cells was investigated by lineage tracing using Dermo1-Cre; ROSAmTmG mice. In experimental models of lung injury by lipopolysaccharide and naphthalene, GFP-labeled Dermo1+ mesenchymal cells were traced during injury repair. In vitro lung explant culture treated with or without lipopolysaccharide was also used to verify in vivo data. Results During injury repair, a subgroup of GFP-labeled Dermo1+ mesenchymal cells were found to contribute to normal repair of the airway epithelium and differentiated into Club cells, ciliated cells, and goblet cells. In Club cell-specific naphthalene injury model, the process of Dermo1+ stem cell regenerating epithelial cells was dissected. The Dermo1+ stem cells was migrated into the airway epithelium layer sooner after injury, and sequentially differentiated transitionally to epithelial stem cells, such as neuroendocrine cells, and finally to newly differentiated Club cells, ciliated cells, and goblet cells in injury repair. Conclusion In this study, a population of Dermo1+ mesenchymal stem cell was identified to serve as stem cells in airway epithelial cell regeneration during injury repair. The Dermo1+ mesenchymal stem cell differentiated into epithelial stem cells before reestablishing various epithelial cells. These findings have implications for understanding the regulation of lung repair and the potential for usage of mesenchymal stem cells in therapeutic strategies for lung diseases.

scholarly journals Contemporary views on inflammatory pain mechanisms: TRPing over innate and microglial pathways

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2425 ◽  
Author(s):  
Zhonghui Guan ◽  
Judith Hellman ◽  
Mark Schumacher
Keyword(s):  
Cellular Response ◽  
Transient Receptor Potential ◽  
Tissue Injury ◽  
Trauma Surgery ◽  
Receptor Potential ◽  
Cell Types ◽  
Metabolic Dysfunction ◽  
Pain Mechanisms ◽  
Transient Receptor

Tissue injury, whether by trauma, surgical intervention, metabolic dysfunction, ischemia, or infection, evokes a complex cellular response (inflammation) that is associated with painful hyperalgesic states. Although in the acute stages it is necessary for protective reflexes and wound healing, inflammation may persist well beyond the need for tissue repair or survival. Prolonged inflammation may well represent the greatest challenge mammalian organisms face, as it can lead to chronic painful conditions, organ dysfunction, morbidity, and death. The complexity of the inflammatory response reflects not only the inciting event (infection, trauma, surgery, cancer, or autoimmune) but also the involvement of heterogeneous cell types including neuronal (primary afferents, sensory ganglion, and spinal cord), non-neuronal (endothelial, keratinocytes, epithelial, and fibroblasts), and immune cells. In this commentary, we will examine 1.) the expression and regulation of two members of the transient receptor potential family in primary afferent nociceptors and their activation/regulation by products of inflammation, 2.) the role of innate immune pathways that drive inflammation, and 3.) the central nervous system’s response to injury with a focus on the activation of spinal microglia driving painful hyperalgesic states.

III. A molecular prelude to intestinal inflammation

1999 ◽  
Vol 276 (4) ◽  
pp. G795-G799 ◽  
Author(s):  
Mark J. S. Miller ◽  
Manuel Sandoval
Keyword(s):  
Nitric Oxide ◽  
Nitrogen Oxides ◽  
Chronic Inflammation ◽  
Intestinal Inflammation ◽  
Tissue Injury ◽  
Direct Interaction ◽  
Oxides Of Nitrogen ◽  
Anti Inflammatory ◽  
Oxide Synthase

Nitric oxide (NO) synthesis is markedly augmented in states of inflammation, largely due to the expression of inducible nitric oxide synthase (iNOS). Although NO has anti-inflammatory consequences under basal conditions, it remains enigmatic as to why NO displays proinflammatory characteristics in chronic inflammation. Either the anti-inflammatory actions are weak and of little consequence or, alternatively, other factors influence the role of NO in chronic inflammation. We propose that the answer to this enigma lies in the conversion of NO to other higher oxides of nitrogen (NO2, nitrogen dioxide; N2O3, dinitrogen trioxide; and ONOO−, peroxynitrite). Emerging therapeutic strategies may be independent of NO synthesis; e.g., antioxidants have no direct interaction with NO but attenuate the levels and activity of higher nitrogen oxides. Thus, whereas iNOS may be a marker for the proinflammatory actions of NO, the species that mediate tissue injury/dysfunction in inflammation are likely to be nitrogen oxides other than NO.

Role of expression IL-23 pathway in myocardial injury after global ischemia and reperfusion/cross talk with IL-17

2020 ◽  
Vol 8 (1) ◽  
pp. 21-33
Author(s):  
Ling Ogiku ◽  
Runqiu Fujii
Keyword(s):  
Epithelial Cells ◽  
Myocardial Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Cell Types ◽  
Global Ischemia ◽  
Neutrophil Accumulation ◽  
Close Proximity

Myocardial injury caused by global ischemia/reperfusion is a complicated pathophysiological course, in which inflammation is thought to play an important role. Endothelial dysfunction plays a critical role in the pathogenesis of reperfusion injury in the myocardium. This role stems from the close proximity of the endothelium to neutrophils and other inflammatory cell types at the vascular interface during the critical early phase as well as the later phase of reperfusion. IL-17A is a cytokine expressed by a variety of cells in response to inflammatory cytokines that are released following tissue injury and/or inflammation. IL-17A induces epithelial cells to secrete neutrophil chemoattractants. The cytokine IL-23, which can be produced by epithelial cells, plays an important role in IL-17A production. Global myocardial injury induced by abdominal heart transplant model in IL-17A deficient (Il17a-/-), IL-23R deficient (Il23r-/-) and WT mice. Our data showed that cTn-I, neutrophil accumulation MCP-1 and ICAM-1 were significantly less in both Il17a-/- mice and Il23r/- mice than in WT controls. These two pathways may become possible therapeutic targets for the treatment of global ischemia induced myocardial injury.

Is astrocyte calcium signaling relevant for synaptic plasticity?

2010 ◽  
Vol 6 (3) ◽  
pp. 147-155 ◽  
Author(s):  
Sarrah Ben Achour ◽  
Lorena Pont-Lezica ◽  
Catherine Béchade ◽  
Olivier Pascual
Keyword(s):  
Synaptic Plasticity ◽  
Calcium Signaling ◽  
Glial Cells ◽  
Direct Interaction ◽  
Cell Types ◽  
Pivotal Role ◽  
Calcium Flux ◽  
Calcium Dependent ◽  
Structural Functions

Astrocytes constitute a major group of glial cells which were long regarded as passive elements, fulfilling nutritive and structural functions for neurons. Calcium rise in astrocytes propagating to neurons was the first demonstration of direct interaction between the two cell types. Since then, calcium has been widely used, not only as an indicator of astrocytic activity but also as a stimulator switch to control astrocyte physiology. As a result, astrocytes have been elevated from auxiliaries to neurons, to cells involved in processing synaptic information. Curiously, while there is evidence that astrocytes play an important role in synaptic plasticity, the data relating to calcium's pivotal role are inconsistent. In this review, we will detail the various mechanisms of calcium flux in astrocytes, then briefly present the calcium-dependent mechanisms of gliotransmitter release. Finally, we will discuss the role of calcium in plasticity and present alternative explanations that could reconcile the conflicting results published recently.

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