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1.
Cell Physiol Biochem ; 54(2): 195-210, 2020 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-32083406

RESUMEN

BACKGROUND/AIMS: Idiopathic pulmonary fibrosis (IPF) is a specific form of progressive and chronic interstitial lung disease of unknown cause. IPF is characterized by excessive deposition of extracellular matrix (ECM) and destructive pathological remodeling due to epithelial-to-mesenchymal transition (EMT). Eventually, lung interstitium thickens and stiffens and breathing becomes difficult. It has been well established that the transforming growth factor-ß1 (TGF-ß1)/Smad signaling pathway plays a critical role in the pathogenesis of pulmonary fibrosis. TGF-ß1-mediated activation of mitogen activated protein kinase (MAPK) family affects Smad signaling. p90RSK is a serine/threonine kinase and is activated by the extracellular signal-regulated kinase (ERK) signaling pathway. However, the roles played by p90RSK in TGF-ß1 signaling and the pathogenesis of pulmonary fibrosis remain unknown. METHODS: We investigated whether p90RSK regulates the pathogenesis of pulmonary fibrosis using in vitro and in vivo systems and Western blotting, real-time quantitative PCR, transcriptional activity assays and immunofluorescence studies. RESULTS: Pharmacological inhibition of p90RSK by FMK or inhibition of p90RSK with adenoviral vector encoding a dominant negative form of p90RSK suppressed TGF-ß1-induced ECM accumulation and EMT in lung epithelial cells and fibroblasts. Interestingly, FMK significantly inhibited TGF-ß1-induced Smad3 nuclear translocation and smad binding element-dependent transcriptional activity, but not Smad3 phosphorylation. Furthermore, in a mouse model of bleomycin-induced lung fibrosis, FMK ameliorated pulmonary fibrosis. CONCLUSION: These findings indicate that p90RSK plays critical roles in pulmonary fibrosis, which suggests it be viewed as a novel therapeutic target for the treatment of lung fibrosis.


Asunto(s)
Proteínas Quinasas S6 Ribosómicas 90-kDa/metabolismo , Proteína smad3/metabolismo , Animales , Cadherinas/genética , Cadherinas/metabolismo , Línea Celular , Transición Epitelial-Mesenquimal/efectos de los fármacos , Matriz Extracelular/metabolismo , Humanos , Isoquinolinas/farmacología , Cetonas/farmacología , Ratones , Ratones Endogámicos C57BL , Fosforilación/efectos de los fármacos , Inhibidor 1 de Activador Plasminogénico/genética , Inhibidor 1 de Activador Plasminogénico/metabolismo , Regiones Promotoras Genéticas/efectos de los fármacos , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , Piridinas/farmacología , Pirroles/farmacología , Proteínas Quinasas S6 Ribosómicas 90-kDa/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Proteína smad3/antagonistas & inhibidores , Proteína smad3/genética , Activación Transcripcional/efectos de los fármacos , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/farmacología , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo
2.
Khirurgiia (Mosk) ; (2): 62-67, 2020.
Artículo en Ruso | MEDLINE | ID: mdl-32105257

RESUMEN

Ventral hernia is still one of the most common reason for scheduled and emergency surgery. The review is designed to reveal relationships between metabolism in extracellular matrix of connective tissue and pathogenesis of ventral hernias. These data will be valuable to develop a personalized approach to the treatment of these patients.


Asunto(s)
Tejido Conectivo , Matriz Extracelular , Hernia Ventral , Tejido Conectivo/metabolismo , Matriz Extracelular/metabolismo , Humanos , Mallas Quirúrgicas
3.
Cancer Immunol Immunother ; 69(2): 285-292, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31897662

RESUMEN

The wide-ranging collection of malignancies arising at the upper aerodigestive tract is categorized as head and neck cancer (HNC), the sixth most prevalent cancer worldwide. Infection with human papillomavirus (HPV) or exposure to carcinogens is the leading causes of HPV+ and HPV- HNCs development, respectively. HPV+ and HPV- HNCs are different in clinical and molecular aspects. Specifically, HPV- HNCs tightly associate with missense mutants of the TP53 gene (encoding for the p53 protein), suggesting a central role for mutant p53 gain-of-function (GOF) in driving tumorigenesis. In contrast, in HPV + HNC, the sequence of TP53 typically remains intact, while the protein is degraded. In tumor cells, the status of the TP53 gene affects the cargo of secreted exosomes. In this review, we describe the accumulated knowledge regarding the involvement of exosomes and p53 on cellular interactions between HPV+ and HPV- HNC cells, and the surrounding tumor microenvironment (TME). Moreover, we envision how TP53 status may determine exosomes cargo in HNC, and, consequently, modify the TME. The potential roles of exosomes described herein are based on both our studies and the studies of others on mutant p53-derived exosomes. Specifically, we showed how exosomes are shed by cancer cells harboring mutant p53 communicate with tumor-associated macrophages in the colon as well as with cancer-associated fibroblasts in the lung, creating immunosuppressive conditions and promoting invasiveness. Altogether, exosomes in HNC in the context of TP53 status are understudied and extensive research is required to shed light on the biology of HPV+ and HPV- HNC.


Asunto(s)
Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Exosomas/metabolismo , Neoplasias de Cabeza y Cuello/etiología , Neoplasias de Cabeza y Cuello/metabolismo , Mutación , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Animales , Susceptibilidad a Enfermedades , Matriz Extracelular/metabolismo , Predisposición Genética a la Enfermedad , Neoplasias de Cabeza y Cuello/patología , Humanos
4.
Anticancer Res ; 40(1): 229-238, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31892571

RESUMEN

BACKGROUND/AIM: We previously reported the potential of aminonaphthoquinone derivatives as therapeutic agents against breast and other oestrogen-responsive tumours when combined with curcumin. This study aimed at screening of novel aminonaphthoquinone derivatives (Rau 008, Rau 010, Rau 015 and Rau 018) combined with curcumin for cytotoxic, anti-angiogenic and anti-metastatic effects on MCF-7 and MDA-MB-231 breast cancer cells. MATERIALS AND METHODS: Cytotoxic and anti-angiogenic effects were analysed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and enzyme-linked immunosorbent assay; while anti-metastatic effects were measured using adhesion assay, Boyden chambers and Matrigel. RESULTS: Curcumin combined with Rau 008 elicited marked cytotoxic effects in MCF-7 cells compared with the individual treatments, whereas when it was combined with Rau 015 and with Rau 018, it displayed similar effects in MDA-MB-231 cells. The anti-angiogenic effect of Rau 015 plus curcumin in MCF-7 cells and Rau 018 plus curcumin in MDA-MB-231 cells was more effective than individual treatments, while the metastatic capability of MDA-MB-231 cells was significantly reduced after treatment with the aminonaphthoquinone-curcumin combinations. CONCLUSION: Aminonaphthoquinones may offer significant promise as therapeutic agents against breast cancer, particularly when combined with curcumin.


Asunto(s)
Neoplasias de la Mama/patología , Curcumina/farmacología , Progresión de la Enfermedad , Naftoquinonas/farmacología , Neoplasias de la Mama/irrigación sanguínea , Neoplasias de la Mama/tratamiento farmacológico , Adhesión Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Curcumina/química , Curcumina/uso terapéutico , Matriz Extracelular/metabolismo , Femenino , Humanos , Células MCF-7 , Naftoquinonas/química , Invasividad Neoplásica , Neovascularización Patológica/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/metabolismo
5.
Cell Prolif ; 53(2): e12760, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31957194

RESUMEN

Fluid in interstitial spaces accounts for ~20% of an adult body weight and flows diffusively for a short range. Does it circulate around the body like vascular circulations? This bold conjecture has been debated for decades. As a conventional physiological concept, interstitial space is a micron-sized space between cells and vasculature. Fluid in interstitial spaces is thought to be entrapped within interstitial matrix. However, our serial data have further defined a second space in interstitium that is a nanosized interfacial transport zone on a solid surface. Within this fine space, fluid along a solid fibre can be transported under a driving power and identically, interstitial fluid transport can be visualized by tracking the oriented fibres. Since 2006, our data from volunteers and cadavers have revealed a long-distance extravascular pathway for interstitial fluid flow, comprising at least four types of anatomic distributions. The framework of each extravascular pathway contains the longitudinally assembled and oriented fibres, working as a fibrorail for fluid flow. Interestingly, our data showed that the movement of fluid in a fibrous pathway is in response to a dynamic driving source and named as dynamotaxis. By analysis of previous studies and our experimental results, a hypothesis of interstitial fluid circulatory system is proposed.


Asunto(s)
Transporte Biológico Activo/fisiología , Transporte Biológico/fisiología , Tejido Conectivo/metabolismo , Líquido Extracelular/metabolismo , Animales , Matriz Extracelular/metabolismo , Humanos
6.
Medicine (Baltimore) ; 99(2): e18676, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31914060

RESUMEN

Adenoid cystic carcinoma (ACC) is one of the most frequent malignancies of salivary glands. The objective of this study was to identify key genes and potential mechanisms during ACC samples.The gene expression profiles of GSE88804 data set were downloaded from Gene Expression Omnibus. The GSE88804 data set contained 22 samples, including 15 ACC samples and 7 normal salivary gland tissues. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were constructed, and protein-protein interaction network of differentially expressed genes (DEGs) was performed by Cytoscape. The top 10 hub genes were analyzed based on Gene Expression Profiling Interactive Analysis. Then, DEGs between ACC samples and normal salivary gland samples were analyzed by gene set enrichment analysis. Furthermore, miRTarBase and Cytoscape were used for visualization of miRNA-mRNA regulatory network. KEGG pathway analysis was undertaken using DIANA-miRPath v3.0.In total, 382 DEGs were identified, including 119 upregulated genes and 263 downregulated genes. GO analysis showed that DEGs were mainly enriched in extracellular matrix organization, extracellular matrix, and calcium ion binding. KEGG pathway analysis showed that DEGs were mainly enriched in p53 signaling pathway and salivary secretion. Expression analysis and survival analysis showed that ANLN, CCNB2, CDK1, CENPF, DTL, KIF11, and TOP2A are all highly expressed, which all may be related to poor overall survival. Predicted miRNAs of 7 hub DEGs mainly enriched in proteoglycans in cancer and pathways in cancer.This study indicated that identified DEGs and hub genes might promote our understanding of molecular mechanisms, which might be used as molecular targets or diagnostic biomarkers for ACC.


Asunto(s)
Carcinoma Adenoide Quístico/genética , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/fisiología , Neoplasias de las Glándulas Salivales/genética , Matriz Extracelular/metabolismo , Ontología de Genes , Redes Reguladoras de Genes , Humanos , MicroARNs/genética , Transcriptoma
7.
Toxicol Lett ; 321: 103-113, 2020 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-31706003

RESUMEN

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with no effective medication. Andrographolide (Andro), extracted from Chinese herbal Andrographis paniculata, could attenuate bleomycin (BLM)-induced pulmonary fibrosis via inhibition of inflammation and oxidative stress, however, the anti-fibrotic mechanisms have not been clarified. Myofibroblasts are the primary cell types responsible for the accumulation of extracellular matrix (ECM) in fibrotic diseases, and targeting fibroblast proliferation and differentiation is an important therapeutic strategy for the treatment of IPF. Hence, this study aimed to investigate the effects of Andro on the fibroblast proliferation and differentiation in the in vivo and in vitro models. The results showed that Andro improved pulmonary function and inhibited BLM-induced fibroblast proliferation and differentiation and ECM deposition in the lungs. In vitro, Andro inhibited proliferation and induced apoptosis of TGF-ß1-stimulated NIH 3T3 fibroblasts and primary lung fibroblasts (PLFs). Andro also inhibited TGF-ß1-induced myofibroblast differentiation and ECM deposition in both cells. We also found that Andro suppressed TGF-ß1-induced Smad2/3 and Erk1/2 activation, suggesting that Smad2/3 and Erk1/2 inactivation mediates Andro-induced effects on TGF-ß1-induced fibroblast proliferation and differentiation. These results indicated that Andro has novel and potent anti-fibrotic effects in lung fibroblasts via inhibition of the proliferation and myofibroblast differentiation of fibroblasts and subsequent ECM deposition, which are modulated by TGF-ß1-mediated Smad-dependent and -independent pathways.


Asunto(s)
Bleomicina , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Diterpenos/farmacología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Fibrosis Pulmonar Idiopática/prevención & control , Pulmón/efectos de los fármacos , Miofibroblastos/efectos de los fármacos , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta1/farmacología , Animales , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Matriz Extracelular/efectos de los fármacos , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Fibrosis Pulmonar Idiopática/inducido químicamente , Fibrosis Pulmonar Idiopática/metabolismo , Fibrosis Pulmonar Idiopática/patología , Pulmón/metabolismo , Pulmón/patología , Masculino , Ratones , Miofibroblastos/metabolismo , Miofibroblastos/patología , Células 3T3 NIH , Ratas Sprague-Dawley , Transducción de Señal
8.
Bioelectromagnetics ; 41(1): 41-51, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31736106

RESUMEN

Magnetic fields (MFs) have been used as an external stimulus to increase cell proliferation in chondrocytes and extracellular matrix (ECM) synthesis of articular cartilage. However, previously published studies have not shown that MFs are homogeneous through cell culture systems. In addition, variables such as stimulation times and MF intensities have not been standardized to obtain the best cellular proliferative rate or an increase in molecular synthesis of ECM. In this work, a stimulation device, which produces homogeneous MFs to stimulate cell culture surfaces was designed and manufactured using a computational model. Furthermore, an in vitro culture of primary rat chondrocytes was established and stimulated with two MF schemes to measure both proliferation and ECM synthesis. The best proliferation rate was obtained with an MF of 2 mT applied for 3 h, every 6 h for 8 days. In addition, the increase in the synthesis of glycosaminoglycans was statistically significant when cells were stimulated with an MF of 2 mT applied for 5 h, every 6 h for 8 days. These findings suggest that a stimulation with MFs is a promising tool that could be used to improve in vitro treatments such as autologous chondrocyte implantation, either to increase cell proliferation or stimulate molecular synthesis. Bioelectromagnetics. 2020;41:41-51 © 2019 Bioelectromagnetics Society.


Asunto(s)
Cartílago Articular/metabolismo , Condrocitos/citología , Condrocitos/metabolismo , Matriz Extracelular/metabolismo , Campos Magnéticos/efectos adversos , Animales , Proliferación Celular , Supervivencia Celular , Células Cultivadas , Células Inmovilizadas , Simulación por Computador , Glicosaminoglicanos/química , Ratas , Ratas Wistar , Propiedades de Superficie , Temperatura Ambiental , Factores de Tiempo
9.
Cancer Sci ; 111(1): 200-208, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31778288

RESUMEN

Integrins are transmembrane proteins that mediate cell adhesion to the extracellular matrix. Integrin α11 (ITGA11) is not expressed in normal alveolar epithelial cells and is a known receptor for collagen. While integrin α11ß1 overexpression in the tumor stroma has been associated with tumor growth and metastatic potential of non-small cell lung cancer (NSCLC), little is known about the role of ITGA11 in tumor cells. Thus, we examined the RNA expression of ITGA11 by quantitative RT-PCR in 80 samples collected from NSCLC patients who had undergone surgical resection and analyzed the clinical outcomes. We found that high expression of ITGA11 was associated with lower recurrence-free survival in all NSCLC patients (P = 0.043) and in stage I NSCLC patients (P = 0.049). These results were consistent with in silico analyses of the Cancer Genome Atlas database. We also analyzed cell proliferation, migration and invasion capacity in lung cancer cell lines after overexpression of ITGA11. Overexpression of ITGA11 in lung cancer cell lines had little effect on cell proliferation but resulted in increased migration and invasion capacity. Our findings suggest that ITGA11 plays a significant role in cancer migration and invasion, leading to higher recurrence. ITGA11 expression may be a predictor of poor prognosis in patients with surgically resected NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Cadenas alfa de Integrinas/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Adulto , Anciano , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Colágeno/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad
10.
Cancer Immunol Immunother ; 69(2): 223-235, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31650200

RESUMEN

The lysyl oxidases (LOXs) are a family of enzymes deputed to cross-link collagen and elastin, shaping the structure and strength of the extracellular matrix (ECM). However, many novel "non-canonical" functions, alternative substrates, and regulatory mechanisms have been described and are being continuously elucidated. The activity of LOXs, therefore, appears to be integrated into a complex network of signals regulating many cell functions, including survival/proliferation/differentiation. Among these signaling pathways, TGF-ß and PI3K/Akt/mTOR, in particular, cross-talk extensively with each other and with LOXs also initiating complex feedback loops which modulate the activity of LOXs and direct the remodeling of the ECM. A growing body of evidence indicates that LOXs are not only important in the homeostasis of the normal structure of the ECM, but are also implicated in the establishment and maturation of the tumor microenvironment. LOXs' association with advanced and metastatic cancer is well established; however, there is enough evidence to support a significant role of LOXs in the transformation of normal epithelial cells, in the accelerated tumor development and the induction of invasion of the premalignant epithelium. A better understanding of LOXs and their interactions with the different elements of the tumor immune microenvironment will prove invaluable in the design of novel anti-tumor strategies.


Asunto(s)
Inmunidad , Neoplasias/etiología , Proteína-Lisina 6-Oxidasa/química , Proteína-Lisina 6-Oxidasa/inmunología , Microambiente Tumoral/inmunología , Animales , Biomarcadores , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Familia de Multigenes , Neoplasias/patología , Transducción de Señal , Relación Estructura-Actividad
11.
Gene ; 729: 144233, 2020 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-31759980

RESUMEN

Collagen ß (1-O) galactosyltransferase 1 (GLT25D1) has been reported to transfer galactose to hydroxylysine residues via ß (1-O) linkages in collagen. However, the role of Glt25d1 in liver fibrogenesis is still unknow. Recently, we generated a Glt25d1 knockout mouse to elucidate the role of Glt25d1 in vivo. However, we found that complete deletion of the Glt25d1 gene resulted in embryonic lethality at E11.5. Histopathological analysis revealed that dysplasia in Glt25d1-/- labyrinth with defects of the vascular network. Immunohistochemical showed that the decrease in proliferation of Glt25d1-/- liver and the developing central nervous system (CNS). The role of Glt25d1 in liver fibrogenesis was explored by Glt25d1+/- mice. Glt25d1+/- mice and wild-type (WT) mice were injected intraperitoneally with the same dose of CCl4. The higher level of serum alanine aminotransferase was observed in Glt25d1+/- mice. Reverse transcription-quantitative polymerase chainreaction demonstrated that the mRNA expression levels of the inflammatory cytokines such as, Tnf-α, Cxcl-1 and Mcp-1, showed a significantly increase in CCl4-treated Glt25d1+/- mice. Collagen-I, collagen-III and α-SMA transcripts accumulation was markedly increased in the Glt25d1+/- mice. However, Masson's trichrome staining revealed a trend to decrease in the ECM proteins deposition of Glt25d1+/- liver. Immunohistochemistry and Western blots revealed that the protein expression of Collagen-III was reduced and a trend to a decrease in collagen-I was observed in the Glt25d1+/- liver compared with those of WT mice. Our results demonstrate that Glt25d1 knockout results in embryonic lethality and down-regulation of Glt25d1 may inhibit collagen secretion during liver fibrogenesis.


Asunto(s)
Colágeno/metabolismo , Galactosiltransferasas/metabolismo , Cirrosis Hepática/metabolismo , Alanina Transaminasa/metabolismo , Animales , Colágeno/antagonistas & inhibidores , Regulación hacia Abajo , Matriz Extracelular/metabolismo , Femenino , Galactosiltransferasas/genética , Glicosilación , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática/genética , Cirrosis Hepática/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Embarazo
12.
J Orthop Res ; 38(1): 192-201, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31444797

RESUMEN

Rotator cuff tears (RCT) is a multifactorial disease with genetic factors contributing for the disease etiology. We hypothesized that genetic variants in genes involved in extracellular matrix (ECM) homeostasis may alter susceptibility to RCT. We evaluated 20 polymorphisms of genes involved in ECM homeostasis in 211 cases of full-thickness tears of the supraspinatus (Nfemales = 130; Nmales = 81) and 567 age-matched controls (Nfemales = 317; Nmales = 250). Multivariate logistic regressions were carried out with age, gender, genetic ancestry (based on the analysis of 61 biallelic short insertion/deletion polymorphisms), and common co-morbidities (diabetes, dyslipidemia, and smoking habits) as covariates. We observed that carriers of the rare allele of both studied variants of TGFB1, as well as their G/A (rs1800470/rs1800469) haplotype, were less susceptible to RCT (p < 0.05). In contrast, carriers of the G allele of MMP9 rs17576 (p = 0.014) or G/G haplotype (rs17576/rs17577; p < 0.001) had an increased risk for tendon tears. The presence of the T allele of MMP2 rs2285053 (p = 0.033), the T allele of MMP3 rs679620 (p = 0.024), and the TT-genotype of TIMP2 rs2277698 (p = 0.01) was associated with susceptibility to tears, especially in females. In males, the A allele of COL5A1 rs3196378 (p = 0.032) and the G allele of TGFBR1 rs1590 (p = 0.039) were independent risk factors for RCT. The C/T COL5A1 (rs3196378/rs11103544) haplotype was associated with a reduced risk of tears in males (p = 0.03). In conclusion, we identified the genetic variants associated with RCT susceptibility, thereby reinforcing the role of genes involved in the structure and homeostasis of the ECM of tendons in disease development. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:192-201, 2020.


Asunto(s)
Matriz Extracelular/metabolismo , Predisposición Genética a la Enfermedad , Homeostasis , Polimorfismo de Nucleótido Simple , Lesiones del Manguito de los Rotadores/genética , Adulto , Anciano , Estudios de Casos y Controles , Colágeno Tipo V/genética , Femenino , Haplotipos , Humanos , Modelos Logísticos , Masculino , Metaloproteinasa 2 de la Matriz/genética , Persona de Mediana Edad , Caracteres Sexuales , Factor de Crecimiento Transformador beta1/genética
13.
Adv Exp Med Biol ; 1131: 1079-1102, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31646546

RESUMEN

In multicellular organisms, the cells are surrounded by persistent, dynamic extracellular matrix (ECM), the largest calcium reservoir in animals. ECM regulates several aspects of cell behavior including cell migration and adhesion, survival, gene expression and differentiation, thus playing a significant role in health and disease. Calcium is reported to be important in the assembly of ECM, where it binds to many ECM proteins. While serving as a calcium reservoir, ECM macromolecules can directly interact with cell surface receptors resulting in calcium transport across the membrane. This chapter mainly focusses on the role of cell-ECM interactions in cellular calcium regulation and how calcium itself mediates these interactions.


Asunto(s)
Calcio , Matriz Extracelular , Animales , Calcio/metabolismo , Movimiento Celular , Matriz Extracelular/metabolismo , Proteínas de la Matriz Extracelular/metabolismo
14.
J Med Life ; 12(3): 225-229, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31666821

RESUMEN

Almost 30 years have passed since the term 'tissue engineering' was created to represent a new concept that focuses on the regeneration of neotissues from cells with the support of biomaterials and growth factors. This interdisciplinary engineering has attracted much attention as a new therapeutic means that may overcome the drawbacks involved in the current artificial organs and organ transplantation that have also been aiming at replacing lost or severely damaged tissues or organs. However, the tissues regenerated by tissue engineering and widely applied to patients are still minimal, including skin, bone, cartilage, capillary, and periodontal tissues. What are the reasons for such slow advances in clinical applications of tissue engineering? This article gives a brief overview of the current state of tissue engineering, covering the fundamentals and applications. The fundamentals of tissue engineering involve cell sources, scaffolds for cell expansion and differentiation, as well as carriers for growth factors. Animal and human trials are a major part of the applications. Based on these results, some critical problems to be resolved for the advances of tissue engineering are addressed from the engineering point of view, emphasizing the close collaboration between medical doctors and biomaterials scientists.


Asunto(s)
Ingeniería de Tejidos/tendencias , Animales , Materiales Biocompatibles/farmacología , Células Madre Embrionarias/efectos de los fármacos , Células Madre Embrionarias/metabolismo , Matriz Extracelular/metabolismo , Humanos , Andamios del Tejido/química
15.
Biochem Soc Trans ; 47(6): 1679-1687, 2019 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-31724697

RESUMEN

Myocardial Infarction (MI) initiates a series of wound healing events that begins with up-regulation of an inflammatory response and culminates in scar formation. The extracellular matrix (ECM) is intricately involved in all stages from initial break down of existing ECM to synthesis of new ECM to form the scar. This review will summarize our current knowledge on the processes involved in ECM remodeling after MI and identify the gaps that still need to be filled.


Asunto(s)
Matriz Extracelular/patología , Infarto del Miocardio/patología , Remodelación Ventricular , Animales , Cicatriz/patología , Matriz Extracelular/metabolismo , Humanos , Inflamación/metabolismo , Infarto del Miocardio/metabolismo , Cicatrización de Heridas
16.
Invest Ophthalmol Vis Sci ; 60(14): 4661-4669, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-31725165

RESUMEN

Purpose: To evaluate the inflammatory cytokine, growth factors, extracellular matrix (ECM) remodeling genes, profibrotic and antifibrotic molecules in patients undergoing glaucoma filtration surgery (GFS). Additionally, the effect of preoperative antiglaucoma medications (AGMs) and postoperative bleb status were related to these parameters. Methods: Tenon's tissue and aqueous humour (AH) were collected from 207 patients undergoing GFS with primary open-angle glaucoma (POAG) (n = 77), primary angle-closure glaucoma (PACG) (n = 62), and cataract controls (n = 68). Monocyte chemoattractant protein-1 (MCP-1), connective tissue growth factor (CTGF), transforming growth factor ß1/2 (TGF-ß1/2), lysyl oxidase (LOX), lysyl oxidase L2 (LOXL2), elastin (ELN), collagen type 1 α 1 (COL1A1), secreted protein acidic and rich in cysteine (SPARC), α-smooth muscle actin (α-SMA), and decorin (DCN) were determined in tenon's tissue by real-time PCR and in AH using ELISA. Results: A significant increase was observed in the transcripts of MCP-1, TGF-ß2, and SPARC in POAG and PACG (P < 0.05); CTGF, TGF-ß1, LOX, LOXL2, ELN, COL1A1, and α-SMA in PACG (P < 0.05) compared with control. DCN transcript was significantly decreased in POAG and PACG (P < 0.05) compared with control. The protein levels of CTGF, TGF-ß1/ß2, ELN, SPARC, and LOXL2 was significantly elevated in POAG and PACG (P < 0.05); DCN was decreased (P < 0.05) compared with control. These parameters showed significant association with duration of preoperative AGMs and postoperative bleb status. Conclusions: This study demonstrates increased expression of growth factors and ECM molecules, both at protein and transcript levels in GFS patients. A decreased DCN in AH seems striking, and if restored might have a therapeutic role in minimizing postoperative scarring to improve GFS outcome.


Asunto(s)
Humor Acuoso/metabolismo , Decorina/metabolismo , Matriz Extracelular/metabolismo , Glaucoma de Ángulo Cerrado/metabolismo , Glaucoma de Ángulo Abierto/metabolismo , Cápsula de Tenon/metabolismo , Anciano , Estudios de Casos y Controles , Factor de Crecimiento del Tejido Conjuntivo/genética , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Citocinas/genética , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Proteínas de la Matriz Extracelular/genética , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Glaucoma de Ángulo Cerrado/cirugía , Glaucoma de Ángulo Abierto/cirugía , Humanos , Masculino , Persona de Mediana Edad , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Trabeculectomía , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismo
17.
Folia Histochem Cytobiol ; 57(4): 157-158, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31743418

RESUMEN

Transforming growth factor-ß (TGF-ß) is an important regulator of many cellular and immunological functions. It is often deposited in extracellular matrices in a latent form. This commentary is to draw attention to the likelihood that preparing cell-free matrices from tissue cultures by high pH buffers, such as ammonium hydroxide, can activate the TGF-ß. Therefore, cells subsequently seeded onto such matrices may respond to the presence of active TGF-ß in addition to interactions with macromolecular extracellular matrix components.


Asunto(s)
Medios de Cultivo/química , Matriz Extracelular/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Hidróxido de Amonio/química , Animales , Técnicas de Cultivo de Célula , Línea Celular , Matriz Extracelular/química , Concentración de Iones de Hidrógeno , Ratones , Visón , Factor de Crecimiento Transformador beta/química
18.
Life Sci ; 239: 117049, 2019 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-31730862

RESUMEN

Cancer associated fibroblasts (CAFs) as the dominant, long-lived and highly plastic cells within the tumor microenvironment (TME) with multi-faceted roles that are endowed with tumor aggressive features. They can instruct and shape the stroma of tumor into being a highly qualified bed for cellular recruitment, differentiation and plasticity in the host tissue or secondary organ/s. In this Review, we have a discussion over CAF reprogramming as a general concept, inducers and outcomes, pursued by suggesting potential strategies to combat this key promoter of tumor.


Asunto(s)
Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/fisiología , Reprogramación Celular/fisiología , Matriz Extracelular/metabolismo , Matriz Extracelular/fisiología , Fibroblastos/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Neoplasias/patología , Células del Estroma/metabolismo , Factores de Crecimiento Transformadores/metabolismo , Factores de Crecimiento Transformadores/fisiología , Microambiente Tumoral
19.
Biochem Soc Trans ; 47(6): 1661-1678, 2019 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-31754702

RESUMEN

The extracellular matrix (ECM) is a fundamental component of tissue microenvironments and its dysregulation has been implicated in a number of diseases, in particular cancer. Tumour desmoplasia (fibrosis) accompanies the progression of many solid cancers, and is also often induced as a result of many frontline chemotherapies. This has recently led to an increased interest in targeting the underlying processes. The major structural components of the ECM contributing to desmoplasia are the fibrillar collagens, whose key assembly mechanism is the enzymatic stabilisation of procollagen monomers by the lysyl oxidases. The lysyl oxidase family of copper-dependent amine oxidase enzymes are required for covalent cross-linking of collagen (as well as elastin) molecules into the mature ECM. This key step in the assembly of collagens is of particular interest in the cancer field since it is essential to the tumour desmoplastic response. LOX family members are dysregulated in many cancers and consequently the development of small molecule inhibitors targeting their enzymatic activity has been initiated by many groups. Development of specific small molecule inhibitors however has been hindered by the lack of crystal structures of the active sites, and therefore alternate indirect approaches to target LOX have also been explored. In this review, we introduce the importance of, and assembly steps of the ECM in the tumour desmoplastic response focussing on the role of the lysyl oxidases. We also discuss recent progress in targeting this family of enzymes as a potential therapeutic approach.


Asunto(s)
Matriz Extracelular/metabolismo , Neoplasias/enzimología , Proteína-Lisina 6-Oxidasa/metabolismo , Animales , Colágeno/metabolismo , Elastina/metabolismo , Matriz Extracelular/enzimología , Matriz Extracelular/patología , Fibrosis , Humanos , Neoplasias/patología , Proteína-Lisina 6-Oxidasa/antagonistas & inhibidores , Microambiente Tumoral
20.
Nat Protoc ; 14(12): 3395-3425, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31705125

RESUMEN

The extracellular matrix (ECM) is a major regulator of homeostasis and disease, yet the 3D structure of the ECM remains poorly understood because of limitations in ECM visualization. We recently developed an ECM-specialized method termed in situ decellularization of tissues (ISDoT) to isolate native 3D ECM scaffolds from whole organs in which ECM structure and composition are preserved. Here, we present detailed surgical instructions to facilitate decellularization of 33 different mouse tissues and details of validated antibodies that enable the visualization of 35 mouse ECM proteins. Through mapping of these ECM proteins, the structure of the ECM can be determined and tissue structures visualized in detail. In this study, perfusion decellularization is presented for bones, skeletal muscle, tongue, salivary glands, stomach, duodenum, jejunum/ileum, large intestines, mesentery, liver, gallbladder, pancreas, trachea, bronchi, lungs, kidneys, urinary bladder, ovaries, uterine horn, cervix, adrenal gland, heart, arteries, veins, capillaries, lymph nodes, spleen, peripheral nerves, eye, outer ear, mammary glands, skin, and subcutaneous tissue. Decellularization, immunostaining, and imaging take 4-5 d.


Asunto(s)
Matriz Extracelular/metabolismo , Imagen Tridimensional/métodos , Coloración y Etiquetado/métodos , Animales , Anticuerpos/metabolismo , Matriz Extracelular/fisiología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Especificidad de Órganos , Perfusión/métodos , Ingeniería de Tejidos/métodos , Andamios del Tejido/química
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