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1.
Nat Commun ; 10(1): 5776, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852888

RESUMO

Skeletal muscle stem cells, called satellite cells and defined by the transcription factor PAX7, are responsible for postnatal muscle growth, homeostasis and regeneration. Attempts to utilize the regenerative potential of muscle stem cells for therapeutic purposes so far failed. We previously established the existence of human PAX7-positive cell colonies with high regenerative potential. We now identified PAX7-negative human muscle-derived cell colonies also positive for the myogenic markers desmin and MYF5. These include cells from a patient with a homozygous PAX7 c.86-1G > A mutation (PAX7null). Single cell and bulk transcriptome analysis show high intra- and inter-donor heterogeneity and reveal the endothelial cell marker CLEC14A to be highly expressed in PAX7null cells. All PAX7-negative cell populations, including PAX7null, form myofibers after transplantation into mice, and regenerate muscle after reinjury. Transplanted PAX7neg cells repopulate the satellite cell niche where they re-express PAX7, or, strikingly, CLEC14A. In conclusion, transplanted human cells do not depend on PAX7 for muscle regeneration.


Assuntos
Moléculas de Adesão Celular/fisiologia , Lectinas Tipo C/fisiologia , Músculo Esquelético/fisiologia , Fator de Transcrição PAX7/genética , Regeneração , Células Satélites de Músculo Esquelético/fisiologia , Síndrome de Emaciação/genética , Animais , Biópsia , Pré-Escolar , Consanguinidade , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Músculo Esquelético/citologia , Músculo Esquelético/lesões , Mutação , Fator de Transcrição PAX7/metabolismo , Cultura Primária de Células , Células Satélites de Músculo Esquelético/transplante , Análise de Célula Única , Transplante Heterólogo/métodos , Síndrome de Emaciação/terapia , Sequenciamento Completo do Exoma
2.
Adv Exp Med Biol ; 1190: 181-198, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31760645

RESUMO

Schmidt-Lanterman incisure (SLI) is a circular-truncated cone shape in the myelin internode that is a specific feature of myelinated nerve fibers formed in Schwann cells in the peripheral nervous system (PNS). The SLI circular-truncated cones elongate like spring at the narrow sites of beaded appearance nerve fibers under the stretched condition. In this chapter, we demonstrate various molecular complexes in SLI, and especially focus on membrane skeleton, protein 4.1G-membrane protein palmitoylated 6 (MPP6)-cell adhesion molecule 4 (CADM4). 4.1G was essential for the molecular targeting of MPP6 and CADM4 in SLI. Motor activity and myelin ultrastructures were abnormal in 4.1G-deficient mice, indicating the 4.1G function as a signal for proper formation of myelin in PNS. Thus, SLI probably has potential roles in the regulation of adhesion and signal transduction as well as in structural stability in Schwann cell myelin formation.


Assuntos
Bainha de Mielina/fisiologia , Sistema Nervoso Periférico/fisiologia , Células de Schwann/fisiologia , Animais , Axônios , Moléculas de Adesão Celular/fisiologia , Guanilato Quinases/fisiologia , Proteínas Ligadas a Lipídeos/fisiologia , Camundongos , Proteínas dos Microfilamentos/fisiologia , Bainha de Mielina/ultraestrutura , Transdução de Sinais
3.
J Biomed Sci ; 26(1): 43, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31167655

RESUMO

BACKGROUND: Stroke is the second most common cause of deaths worldwide. After an ischemic stroke, the proliferated reactive astrocytes in the peri-infarct areas play a beneficial role in neuronal survival. As such, astrocytes have gradually become a target for neuroprotection in stroke. The present study assessed the hypothesis that Pinin (Pnn), originally identified as a nuclear and desmosome-associated protein and is now known to possess anti-apoptotic capacity, protects astrocytes from cell death after ischemic stroke and delineated the underlying mechanisms. METHODS: In in vivo experiments, adult male Sprague-Dawley rats (12-week old) were used to induce acute focal cerebral ischemia employing the middle cerebral artery occlusion (MCAO) method. In in vitro experiments, postnatal day 1 (P1) Sprague-Dawley rat pups were used to prepare cultures of primary astrocytes. Oxygen-glucose deprivation (OGD) and re-oxygenation (OGD/R) procedures were employed to mimic the hypoxic-ischemic condition of stroke in those astrocytes. RESULTS: We found in the peri-infarct area of the ipsilateral cortex and striatum in Sprague-Dawley rats after transient MCAO an increase in Pnn expression that correlated positively with the time-course of infarction as detected by T2-weighted imaging and triphenyltetrazolium chloride staining, augmented number of reactive astrocytes that double-labelled with Pnn as determined by immunofluorescence, and enhanced cytotoxic edema as revealed by diffusion weighted imaging; but mirrored the decreased cleaved caspase-3 as measured by western blot. In an OGD and OGD/R model using primary cultured astrocytes, treatment with Pnn siRNA doubled the chance of surviving astrocytes to manifest cell death as revealed by flow cytometry, and blunted activated ERK signaling, reduced Bcl-2 expression and augmented cleaved caspase 3 detected by western blot in the normoxia, OGD or OGD/R group. Gene-knockdown of Pnn also impeded the reversal from decline in cell viability, elevation in lactate dehydrogenase leakage and decrease in ATP production in the OGD/R group. CONCLUSION: We conclude that the endogenous Pnn participates in neuroprotection after acute ischemic stroke by preserving the viability of astrocytes that survived the ischemic challenge via maintenance of mitochondrial anti-apoptotic and bioenergetics functions.


Assuntos
Proteínas Reguladoras de Apoptose/fisiologia , Apoptose/fisiologia , Astrócitos/patologia , Isquemia Encefálica/patologia , Moléculas de Adesão Celular/fisiologia , Mitocôndrias/metabolismo , Acidente Vascular Cerebral/patologia , Animais , Apoptose/genética , Proteínas Reguladoras de Apoptose/genética , Moléculas de Adesão Celular/genética , Morte Celular/genética , Morte Celular/fisiologia , Sobrevivência Celular , Masculino , Mitocôndrias/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
4.
Clin Sci (Lond) ; 133(11): 1215-1228, 2019 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-31101724

RESUMO

Background: Although junctional adhesion molecule-like protein (JAML) has recently been implicated in leukocyte recruitment during inflammation and wound repair, its role in atherosclerosis remains to be elucidated. Methods and results: First, we showed that JAML was strongly expressed in atherosclerotic plaques of cardiovascular patients. Similar results were obtained with atherosclerotic plaques of ApoE-/- mice. Co-immunofluorescence staining showed that JAML was mainly expressed in macrophages. Enhanced expression of JAML in cultured macrophages was observed following exposure of the cells to oxLDL. The functional role of JAML in atherosclerosis and macrophages function was assessed by interference of JAML with shRNA in vivo and siRNA in vitro Silencing of JAML in mice significantly attenuated atherosclerotic lesion formation, reduced necrotic core area, increased plaque fibrous cap thickness, decreased macrophages content and inflammation. In addition, histological staining showed that JAML deficiency promoted plaques to stable phenotype. In vitro, JAML siRNA treatment lowered the expression of inflammatory cytokines in macrophages treated with oxLDL. The mechanism by which JAML mediated the inflammatory responses may be related to the ERK/NF-κB activation. Conclusions: Our results demonstrated that therapeutic drugs which antagonize the function of JAML may be a potentially effective approach to attenuate atherogenesis and enhance plaque stability.


Assuntos
Aterosclerose/metabolismo , Moléculas de Adesão Celular/metabolismo , Camundongos Knockout para ApoE/metabolismo , Placa Aterosclerótica/metabolismo , Animais , Apolipoproteínas E/metabolismo , Apolipoproteínas E/fisiologia , Aterosclerose/etiologia , Western Blotting , Moléculas de Adesão Celular/fisiologia , Imunofluorescência , Inativação Gênica , Humanos , Moléculas de Adesão Juncional , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células RAW 264.7 , RNA Interferente Pequeno/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
5.
Infect Immun ; 87(8)2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31085704

RESUMO

Salmonella enterica serovar Typhimurium, a Gram-negative bacterium, can cause infectious diseases ranging from gastroenteritis to systemic dissemination and infection. However, the molecular mechanisms underlying this bacterial dissemination have yet to be elucidated. A study indicated that using the lipopolysaccharide (LPS) core as a ligand, S Typhimurium was able to bind human dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (hCD209a), an HIV receptor that promotes viral dissemination by hijacking antigen-presenting cells (APCs). In this study, we showed that S Typhimurium interacted with CD209s, leading to the invasion of APCs and potentially the dissemination to regional lymph nodes, spleen, and liver in mice. Shielding of the exposed LPS core through the expression of O-antigen reduces dissemination and infection. Thus, we propose that similar to HIV, S Typhimurium may also utilize APCs via interactions with CD209s as a way to disseminate to the lymph nodes, spleen, and liver to initiate host infection.


Assuntos
Moléculas de Adesão Celular/fisiologia , Lectinas Tipo C/fisiologia , Receptores de Superfície Celular/fisiologia , Salmonella typhimurium/patogenicidade , Animais , Células Apresentadoras de Antígenos/microbiologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Lipopolissacarídeos/fisiologia , Mananas/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Antígenos O/fisiologia , Nódulos Linfáticos Agregados/fisiologia , Fagocitose , Células RAW 264.7
6.
World J Microbiol Biotechnol ; 35(6): 85, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31134456

RESUMO

Surface properties like hydrophobicity, aggregation ability, adhesion to mucosal surfaces and epithelial cells and transit time are key features for the characterization of probiotic strains. In this study, we used two Lactobacillus paracasei subsp. paracasei strains (BGNJ1-64 and BGSJ2-8) strains which were previously described with very strong aggregation capacity. The aggregation promoting factor (AggLb) expressed in these strains showed high level of binding to collagen and fibronectin, components of extracellular matrix. The working hypothesis was that strains able to aggregate have an advantage to resist in intestinal tract. So, we assessed whether these strains and their derivatives (without aggLb gene) are able to bind or not to intestinal components and we compared the transit time of each strains in mice. In that purpose parental strains (BGNJ1-64 and BGSJ2-8) and their aggregation negative derivatives (BGNJ1-641 and BGSJ2-83) were marked with double antibiotic resistance in order to be tracked in in vivo experiments in mice. Comparative analysis of binding ability of WT and aggregation negative strains to different human intestinal cell lines and mucin revealed no significant difference among them, excluding involvement of AggLb in interaction with surface of intestinal cells and mucin. In vivo experiments showed that surviving and transit time of marked strains in mice did not drastically depend on the presence of the AggLb aggregation factor.


Assuntos
Moléculas de Adesão Celular/metabolismo , Células Epiteliais/microbiologia , Intestinos/microbiologia , Lactobacillus paracasei/crescimento & desenvolvimento , Lactobacillus paracasei/fisiologia , Ligação Proteica , Animais , Aderência Bacteriana/fisiologia , Células CACO-2 , Moléculas de Adesão Celular/fisiologia , Colágeno/metabolismo , Fibronectinas/metabolismo , Células HT29 , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Interações Hidrofóbicas e Hidrofílicas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mucinas/metabolismo , Probióticos , Análise de Onda de Pulso , Propriedades de Superfície
7.
Adv Exp Med Biol ; 1132: 3-4, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037619

RESUMO

The history of periostin and the mechanism of periostin in fibrillogenesis are described. Periostin is a matricellular protein and involved in incurable diseases.


Assuntos
Moléculas de Adesão Celular/fisiologia , Humanos
8.
Adv Exp Med Biol ; 1132: 35-41, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037622

RESUMO

Cardiac muscle (the myocardium) is a unique arrangement of atria and ventricles that are spatially and electrically separated by a fibrous border. The spirally-arranged myocytes in both left and right ventricles are tethered by the component molecules of the cardiac extracellular matrix (ECM), including fibrillar collagen types I and III. Loss of normal arrangement of the ECM with either too little (as is observed in acute myocardial infarction) or too much (cardiac fibrosis in chronic post-myocardial infarction) is the primary contributor to cardiac dysfunction and heart failure. Matricellular proteins exist as non-structural signaling moieties in the ECM, and in the context of cardiac hypertrophy and heart failure, secreted 90 kDa periostin protein has attracted intense scrutiny during the past decade. Secreted periostin is now recognized for its important role in ECM development and maturation, as well as cellular adhesion. The novel mechanisms of periostin function include its role as a mediator of cell-to-matrix signaling, cell survival, and epithelial-mesenchymal transition (EMT). A number of recent studies have examined the hypothesis that periostin is a major contributor to ECM remodeling in the heart, and a number of very recent studies underscore its important role. This review examines recent developments in the mechanisms of periostin function in the normal heart and vasculature, and discusses recent advances which underpin its putative role in the development of cardiovascular disease. Periostin expression is very low at baseline in healthy tissues, but is re-expressed in damaged heart and in vessel walls after injury, in activated cardiac myofibroblasts and vascular smooth muscle cells, respectively. For this reason, periostin may be exploited for investigation of mechanisms of cardiac fibrosis , and we speculate that data generated from studies utilizing this approach may shed light on the timing for application of periostin-specific therapies to quell cardiac fibrosis and associated cardiac dysfunction.


Assuntos
Moléculas de Adesão Celular/fisiologia , Infarto do Miocárdio , Miofibroblastos/citologia , Remodelação Ventricular , Proteínas da Matriz Extracelular , Ventrículos do Coração , Humanos , Miocárdio , Fenótipo
9.
Adv Exp Med Biol ; 1132: 43-47, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037623

RESUMO

Periostin is specifically expressed in periosteum that functions in bone modeling and remodeling and bone repair, and is sensitive to mechanical stress. Thus periostin has been expected for controlling these crucial systems in bone. The results from periostin deficient mice demonstrate that periostin acts on bone remodeling though detailed mechanisms are unknown. Recent findings have revealed that periostin is essential for bone repair. In this chapter, I introduce expression and function of periostin in bone.


Assuntos
Remodelação Óssea , Moléculas de Adesão Celular/fisiologia , Periósteo/fisiologia , Animais , Camundongos
10.
Adv Exp Med Biol ; 1132: 49-61, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037624

RESUMO

Bone regeneration is an efficient regenerative process depending on the recruitment and activation of skeletal stem cells that allow cartilage and bone formation leading to fracture consolidation. Periosteum, the tissue located at the outer surface of bone is now recognized as an essential player in the bone repair process and contains skeletal stem cells with high regenerative potential. The matrix composition of the periosteum defines its roles in bone growth, in cortical bone modeling and remodeling in response to mechanical strain, and in bone repair. Periostin is a key extracellular matrix component of the periosteum involved in periosteum functions. In this chapter, we summarize the current knowledge on the bone regeneration process, the role of the periosteum and skeletal stem cells, and Periostin functions in this context. The matricellular protein Periostin has several roles through all stages of bone repair: in the early days of repair during the initial activation of stem cells within periosteum, in the active phase of cartilage and bone deposition in the facture callus, and in the final phase of bone bridging and reconstitution of the stem cell pool within periosteum.


Assuntos
Regeneração Óssea , Moléculas de Adesão Celular/fisiologia , Periósteo/fisiologia , Cartilagem/fisiologia , Humanos , Osteogênese , Células-Tronco/citologia
11.
Adv Exp Med Biol ; 1132: 63-72, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037625

RESUMO

The goal of periodontal regeneration therapy is to reliably restore teeth's supporting periodontal tissue, while aiding the formation of new connective tissue attached to the periodontal ligament (PDL) fibers and new alveolar bone. Periostin is a matricellular protein, primarily expressed in the periosteum and PDL of adult mice. Its biological functions have been extensively studied in the fields of cardiovascular physiology and oncology. Despite being initially identified in bone and dental tissue, the function of Periostin in PDL and the pathophysiology associated with alveolar bone are scarcely studied. Recently, several studies have suggested that Periostin may be an important regulator of periodontal tissue formation. By promoting collagen fibrillogenesis and the migration of fibroblasts and osteoblasts, Periostin might play a key role in the regeneration of PDL and alveolar bone after periodontal surgery. In this chapter, the implications of Periostin in periodontal tissue biology and its potential use in periodontal tissue regeneration are reviewed.


Assuntos
Moléculas de Adesão Celular/fisiologia , Periodonto/fisiologia , Regeneração , Animais , Humanos , Camundongos , Osteoblastos , Ligamento Periodontal/fisiologia , Dente
12.
Adv Exp Med Biol ; 1132: 73-78, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037626

RESUMO

Periostin is a secreted matricellular protein that primarily interacts with type I collagen and fibronectin extracellular matrix proteins, and is widely distributed in tissues rich in collagen-rich connective tissues, including the periodontal ligament. Its expression in these tissues is especially regulated by mechanical load. While the expression and regulation of periostin in the teeth of murine models and cell lines is well known, its presence in human teeth is poorly documented. Here we update and summarize the available data on the distribution of periostin in the human periodontal ligament, gingiva and dental pulp.


Assuntos
Moléculas de Adesão Celular/fisiologia , Polpa Dentária/fisiologia , Gengiva/fisiologia , Ligamento Periodontal/fisiologia , Dente , Animais , Proteínas da Matriz Extracelular , Humanos , Camundongos
13.
Adv Exp Med Biol ; 1132: 89-98, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037628

RESUMO

Skin is a large organ that is susceptible to damage by external forces, chronic inflammation, and autoimmune reactions. In general, tissue damage causes alterations in both the configuration and type of cells in lesional skin. This phenomenon, called tissue remodeling, is a universal biological response elicited by programmed cell death, inflammation, immune disorders, and tumorigenic, tumor proliferative, and cytoreductive activity. During this process, changes in the components that comprise the extracellular matrix are required to provide an environment that facilitates tissue remodeling. Among these extracellular matrix components, periostin (a glycoprotein secreted predominantly by dermal fibroblasts) has attracted much attention. In normal skin, periostin localizes mainly in the papillary dermis and basement membrane of the epidermis. However, it is expressed at higher levels in the dermis of lesional skin of those with atopic dermatitis, scars, systemic/limited scleroderma, melanoma, and cutaneous T cell lymphoma; expression is also increased by damage caused by allergic/autoimmune responses. Furthermore, periostin induces processes that result in development of dermal fibrosis; it also activates or protracts the immune response. The aim of this review is to summarize recent knowledge about the role of periostin in the pathogenesis of dermatoses.


Assuntos
Moléculas de Adesão Celular/fisiologia , Dermatopatias/patologia , Dermatite Atópica , Fibroblastos , Humanos , Melanoma , Pele
14.
Adv Exp Med Biol ; 1132: 99-112, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037629

RESUMO

Periostin is a matricellular protein that is expressed in several tissues during embryonic development; however, its expression in adults is mostly restricted to collagen-rich connective tissues. Periostin is expressed only briefly during kidney development, but it is not normally detected in the adult kidney. Recent evidence has revealed that periostin is aberrantly expressed in several forms of chronic kidney disease (CKD), and that its expression correlates with the degree of interstitial fibrosis and the decline in renal function. Polycystic kidney disease (PKD), a genetic disorder, is characterized by the formation of numerous fluid-filled cysts in the kidneys. Periostin is secreted by the cyst epithelial cells and accumulates within the extracellular matrix adjacent to the cysts. In PKD mice, periostin overexpression accelerates cyst growth and contributes to structural changes in the kidneys, including interstitial fibrosis. Recent evidence suggests that periostin is a tissue repair molecule; however, its role in repair following acute kidney injury has not been investigated. It is thought that persistent expression of this protein in CKD contributes importantly to tubulointerstitial fibrosis and the progressive decline in renal function. Future studies to define the diverse actions of periostin during kidney injury may lead to effective therapies to slow PKD progression and possibly prevent the development of CKD. This chapter reviews the current literature on the expression of periostin in PKD and other forms of CKD, mechanisms for periostin stimulated cyst growth, its potential role in extracellular matrix production and renal fibrosis, and the evidence for periostin as a novel biomarker for kidney disease.


Assuntos
Moléculas de Adesão Celular/fisiologia , Rim/fisiologia , Insuficiência Renal Crônica/fisiopatologia , Animais , Matriz Extracelular , Fibrose , Humanos , Rim/patologia , Camundongos , Doenças Renais Policísticas/fisiopatologia
15.
Adv Exp Med Biol ; 1132: 113-124, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037630

RESUMO

The transparency of the eye can be disturbed by several eye diseases. It has recently been reported that periostin plays pivotal roles in the pathogenesis of several eye disease, such as diabetic retinopathy (DR), age-related macular degeneration (AMD), glaucoma, pterygia, corneal dystrophy, and chronic ocular allergic diseases. In these diseases, formation of fibro (vascular) tissue plays an important role. Gene expression profiling of human retinal fibro (vascular) membrane revealed significant up-regulation of periostin. The expression of periostin after environmental perturbations, including IL-4 and/or IL-13 induction, can alter normal physiological interactions among fibroblasts, macrophages and ECM protein in the eye. Modulating the expression of periostin by low-molecular weight compounds, antibodies or RNAi directed against the molecule could be a novel therapeutic strategy for inhibiting the progression of those periostin-involved eye diseases.


Assuntos
Moléculas de Adesão Celular/fisiologia , Oftalmopatias/fisiopatologia , Retinopatia Diabética , Humanos , Degeneração Macular , Interferência de RNA
16.
Adv Exp Med Biol ; 1132: 125-136, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037631

RESUMO

Extracellular matrix protein periostin is highly expressed in various tumors and plays a critical role in tumor development and progression. Periostin is mainly secreted by stromal cells such as cancer-associated fibroblasts, myofibroblasts, osteoblasts and bone marrow-derived mesenchymal stromal cells. But in some cases, tumor cells, especially cancer stem cells, can also produce periostin. Periostin has been shown to regulate multiple biological behaviors of tumor cells, including proliferation, survival, invasion, angiogenesis, metastasis and chemoresistance. Moreover, an excessive periostin deposition exerts a pivotal role in remodeling various tumor microenvironments, such as cancer stem cell niche, perivascular niche, premetastatic niche, immunosuppressive microenvironment, bone marrow microenvironment and other tumor growth-supportive microenvironments. In this review, we provide an update understanding of the multifaceted functions and mechanisms of periostin in tumor development and progression.


Assuntos
Moléculas de Adesão Celular/fisiologia , Neoplasias/patologia , Células-Tronco Neoplásicas , Células Estromais , Microambiente Tumoral , Humanos , Nicho de Células-Tronco
17.
Adv Exp Med Biol ; 1132: 139-142, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037632

RESUMO

In addition to main types of fibrosis, other types of fibrosis in incredible diseases have been reported. Among them, liver fibrosis, stroke, and rhinosinusitis are described as new cases of periostin action. To understand periostin function in a new area of fibrosis linked with inflammation, periostin can be used as a new tool to elucidate the mechanisms of unknown diseases.


Assuntos
Moléculas de Adesão Celular/fisiologia , Cirrose Hepática/patologia , Sinusite/patologia , Acidente Vascular Cerebral/patologia , Fibrose , Humanos , Inflamação/patologia
18.
Adv Exp Med Biol ; 1132: 163-176, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037634

RESUMO

Stem cell function is regulated by a huge repertoire of external cues along with stem cell intrinsic genetic and epigenetic factors. These interactions come through a variety of cell adhesion receptors, of which integrins are one of the most important classes. They interact with extracellular matrix (ECM) components and various bound proteins. Apart from inside-out signaling through which integrins ensure that the cells are stably bound to the ECM, outside-in integrin signaling, through binding to a variety of ligands, play important roles in cell fate decisions. Periostin is one such ligand whose role in functional regulation of stem cells is emerging due to its wide expression profile. In this review, we discuss the recent advancements made in the field.


Assuntos
Moléculas de Adesão Celular/fisiologia , Integrinas/fisiologia , Transdução de Sinais , Células-Tronco/citologia , Adesão Celular , Matriz Extracelular , Humanos
19.
Adv Exp Med Biol ; 1132: 177-191, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037635

RESUMO

Although periostin plays a significant role in adult cardiac remodeling diseases, the focus of this review is on periostin as a valvulogenic gene. Periostin is expressed throughout valvular development, initially being expressed in endocardial endothelial cells that have been activated to transform into prevalvular mesenchyme termed "cushion tissues" that sustain expression of periostin throughout their morphogenesis into mature (compacted) valve leaflets. The phenotype of periostin null indicates that periostin is not required for endocardial transformation nor the proliferation of its mesenchymal progeny but rather promotes cellular behaviors that promote migration, survival (anti-apoptotic), differentiation into fibroblastic lineages, collagen secretion and postnatal remodeling/maturation. These morphogenetic activities are promoted or coordinated by periostin signaling through integrin receptors activating downstream kinases in cushion cells that activate hyaluronan synthetase II (Akt/PI3K), collagen synthesis (Erk/MapK) and changes in cytoskeletal organization (Pak1) which regulate postnatal remodeling of cells and associated collagenous matrix into a trilaminar (zonal) histoarchitecture. Pak1 binding to filamin A is proposed as one mechanism by which periostin supports remodeling. The failure to properly remodel cushions sets up a trajectory of degenerative (myxomatous-like) changes that over time reduce biomechanical properties and increase chances for prolapse, regurgitation or calcification of the leaflets. Included in the review are considerations of lineage diversity and the role of periostin as a determinant of mesenchymal cell fate.


Assuntos
Moléculas de Adesão Celular/fisiologia , Valvas Cardíacas/crescimento & desenvolvimento , Organogênese , Diferenciação Celular , Células Endoteliais/citologia , Humanos , Integrinas , Mesoderma/citologia
20.
Adv Exp Med Biol ; 1132: 207-210, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31037637

RESUMO

Since periostin is expressed and functioned in incredible diseases , clinical applications have been initiated to directly target periostin for inhibition or activation, or periostin expression is utilized to indicate the disease state or a marker for curing diseases, which will provide novel methods in clinical applications.


Assuntos
Moléculas de Adesão Celular/fisiologia , Terapia de Alvo Molecular , Biomarcadores , Doença , Humanos
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