DigitalUM :: Browsing by Subject "Extracellular matrix"

Browsing by Subject "Extracellular matrix"

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Open Access
Changes in vascular extracellular matrix composition during decidual spiral arteriole remodeling in early human pregnancy
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Smith, Samantha D.; Choudhury, Ruhul H.; Matos, Patricia; Horn, James A.; Lye, Stephen J.; Dunk, Caroline E.; Aplin, John D.; Jones, Rebecca L.; Harris, Lynda K
Uterine spiral arteriole (SA) remodeling in early pregnancy involves a coordinated series of events including decidual immune cell recruitment, vascular cell disruption and loss, and colonization by placentalderived extravillous trophoblast (EVT). During this process, decidual SA are converted from narrow, muscular vessels into dilated channels lacking vasomotor control. We hypothesized that this extensive alteration in SA architecture must require significant reorganization and/or breakdown of the vascular extracellular matrix (ECM). First trimester decidua basalis (30 specimens) was immunostained to identify spiral arterioles undergoing trophoblast-independent and -dependent phases of remodeling. Serial sections were then immunostained for a panel of ECM markers, to examine changes in vascular ECM during the remodeling process. The initial stages of SA remodeling were characterized by loss of laminin, elastin, fibrillin, collagen types III, IV and VI from the basement membrane, vascular media and/or adventitia, and surrounding decidual stromal cells. Loss of ECM correlated with disruption and disorganization of vascular smooth muscle cells, and the majority of changes occurred prior to extensive colonization of the vessel wall by EVT. The final stages of SA remodeling, characterized by the arrival of EVT, were associated with the increased mural deposition of fibronectin and fibrinoid. This study provides the first detailed analysis of the spatial and temporal loss of ECM from the walls of remodeling decidual SA in early pregnancy.
Open Access
Characterization of organotypic keratinocyte cultures on de-epithelialized bovine tongue mucosa
(Murcia : F. Hernández, 2002) Hildebrand, H.C.; Häkkinen, L.; Wiebe, C.B.; Larjava, H.S.
Organotypic cultures have been used to study epithelial cell behavior for many years. The aim of this study was to develop an organotypic culture method that better mimics the three-dimensional morphology of interdigitating rete ridges and connective tissue papillae and that also conserves the basement membrane zone (BMZ). Bovine tongue mucosa connective tissue, separated from epithelium after 1M NaCl incubation, was used as o rganotypic culture substratum for different human keratinocyte cell lines. Organotypic cultures were characterized by electron and immunofluorescence microscopy for expression of integrin subunits and extracellular matrix components. While spontaneously immortalized mucosal keratinocytes produced highly irregular stratified organotypic cultures, the normal human epidermal keratinocytes (NHEK) demonstrated culture morphology that resembled in vivo epidermis. However, in this model, the histomorphology, expression of differentiation markers involucrin, keratin 10 and 14, and integrins varied significantly between the cell lines. Some cultures appeared to have an extended survival since they were maintained up to 40 days without histological signs of degeneration. The ultrastructure of the BMZ including hemidesmosomes was similar to the normal dermo-epidermal junction. Extracellular matrix molecules, including tenascin, laminin-1 and -5, were expressed in the cultures demonstrating their secretion solely by keratinocytes. Distribution and expression of integrins in NHEK cultures was similar to that seen in vivo skin with the exception of additional expression of a5ß1 and avß6 integrins. Organotypic NHEK cultures show similarities to normal stratified epithelium and are potentially useful for multiple applications for studies on epithelial cell behavior in vitro.
Open Access
Dynamic interactions of the extracellular matrix
(Murcia : F. Hernández, 1996) Slater, M.
The extracellular matrix (ECM) is a dynamic assemblage of interacting molecules that reorganise and regulate cell functions in response to endogenous and exogenous stimulii. Matrix components may affect cell behaviour directly or indirectly through growth factor sequestration and transmembrane signalling, by controlling the speed of various molecules through the ECM, and the access of growth factors, hormones and neurotransmitters to the cell surface.
Open Access
Ex vivo and in vivo modulatory effects of umbilical cord Wharton’s jelly stem cells on human oral mucosa stroma substitutes
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2015) Alfonso-Rodríguez, C.A.; González-Andrades, E.; Jaimes-Parra, B.D.; Fernández-Valadé, R. s; Campos, A.; Sánchez-Quevedo, M. C.; Alaminos, M.; Garzon, I.
Novel oral mucosa substitutes have been developed in the laboratory using human umbilical cord Wharton’s jelly stem cells -HWJSC- as an alternative cell source. In the present work, we have generated human oral mucosa substitutes with oral mucosa keratinocytes and HWJSC to determine the influence of these cell sources on stromal differentiation. First, acellular and cellular stroma substitutes and bilayered oral mucosa substitutes with an epithelial layer consisting of oral mucosa keratinocytes -OM samplesor HWJSC -hOM- were generated. Then, tissues were analyzed by light and electron microscopy, histochemistry and immunohistochemistry to quantify all major extracellular matrix components after 1, 2 and 3 weeks of ex vivo development, and OM and hOM were also analyzed after in vivo grafting. The results showed that bioengineered oral mucosa stromas displayed an adequate fibrillar mesh. Synthesis of abundant collagen fibers was detected in OM and hOM after 3 weeks, and in vivo grafting resulted in an increased collagen synthesis. No elastic or reticular fibers were found. Glycoprotein synthesis was found at the epithelialstromal layer when samples were grafted in vivo. Finally, proteoglycans, decorin, versican and aggrecan were strongly dependent on the in vivo environment and the presence of a well-structured epithelium on top. The use of HWJSC was associated to an increased synthesis of versican. These results confirm the usefulness of fibrinagarose biomaterials for the generation of an efficient human oral mucosa stroma substitute and the importance of the in vivo environment and the epithelialmesenchymal interaction for the adequate differentiation of the bioengineered stroma.
Open Access
Extracellular matrix components in atherosclerotic arteries of Apo E/LDL receptor deficient mice: An immunohistochemical study
(Murcia : F. Hernández, 2004) Ström, Å.; Ahlqvist, E.; Franzé, Adela; Heinegård, D.; Hultghrdh-Nilsson, A.
During accelerated vascular remodeling such as in atherosclerosis, the composition of the extracellular matrix becomes altered. The matrix components of the diseased artery influence cellular processes such as adhesion, migration and proliferation. Furthermore, in atherosclerosis, the inability of the cells within the lesion to produce a mechanically stable matrix may lead to plaque rupture. In this immunohistochemical study of atherosclerotic mice aorta, we have reviewed the presence of ECM components with roles in maintaining tissue structure and function. These components include osteopontin and COMP as well as the leucine rich repeats proteins decorin, PRELP, and fibromodulin. Immunohistochemistry demonstrated presence of osteopontin, COMP, decorin, PRELP and fibromodulin in lesion areas of ApoE/LDLr deficient mice. Some advanced lesions exhibited areas of cartilage-like morphology and were shown to represent cartilage by their content of the cartilage specific proteins collagen II and aggrecan. The results suggest that cartilageassociated cell/collagen binding ECM proteins may be involved in the pathogenesis of atherosclerosis.
Open Access
Integrated extracellular matrix signaling in mammary gland development and breast cancer progression
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2014) Zhu, Jieqing; Xiong, Gaofeng; Trinkle, Christine; Xu, Ren
Extracellular matrix (ECM), a major component of the cellular microenvironment, plays critical roles in normal tissue morphogenesis and disease progression. Binding of ECM to membrane receptor proteins, such as integrin, discoidin domain receptors, and dystroglycan, elicits biochemical and biomechanical signals that control cellular architecture and gene expression. These ECM signals cooperate with growth factors and hormones to regulate cell migration, differentiation, and transformation. ECM signaling is tightly regulated during normal mammary gland development. Deposition and alignment of fibrillar collagens direct migration and invasion of mammary epithelial cells during branching morphogenesis. Basement membrane proteins are required for polarized acinar morphogenesis and milk protein expression. Deregulation of ECM proteins in the long run is sufficient to promote breast cancer development and progression. Recent studies demonstrate that the integrated biophysical and biochemical signals from ECM and soluble factors are crucial for normal mammary gland development as well as breast cancer progression.
Open Access
Integrin-mediated signal transduction pathways
(Murcia : F. Hernández, 1999) Cary,L.A.; Han, D.C.; Guan, J.L.
Integrins serve as adhesion receptors for extracellular matrix proteins and also transduce biochemical signals into the cell. They regulate a variety of cellular functions, including spreading, migration, proliferation and apoptosis. Many signaling pathways downstream of integrins have been identified and characterized and are discussed here. In particular, integrins regulate many protein tyrosine kinases and phosphatases, such as FAK and Src, to coordinate many of the cell processes mentioned above. The regulation of MAP kinases by integrins is important for cell growth or other functions, and the putative roles of Ras and FAK in these pathways are discussed. Phosphatidylinositol lipids and their modifying enzymes, particularly PI 3-kinase, are strongly implicated as mediators of integrinregulated cytoskeletal changes and cell migration. Similarly, actin cytoskeleton regulation by the Rho family of GTPases is coordinated with integrin signaling to regulate cell spreading and migration, although the exact relationship between these pathways is not clear. Finally, intracellular pH and calcium fluxes by integrins are suggested to affect a variety of cellular proteins and functions.
Open Access
Lymphocyte interactions with the extracellular matrix of malignant cells in vítro: A morphological and immunocytochemical study
(Murcia : F. Hernández, 1993) Logothetou-Rella, H.
The interactions of lymphocytes with the glycosaminoglycans-protease-membrane extracellular matrix, produced by mixed cell cultures of normal with malignant cell clones, were examined. Pre-activated and activated heterologous peripheral lymphocytes were used. Co-cultures of activated lymphocytes with al1 cell types used, formed identical cell nodules. Histology of cell nodules showed that activated lymphocytes were cytolytic to pure normal or malignant cell clones. On the contrary, lymphocytes in nodules with mixed cell clones (normal with malignant cell clones) or embryonic cells, underwent degeneration changing the fusiform type tumor nodule into the adenoid type. The adenoid type cell nodule consisted of cells with high nuclear to cytoplasm ratio and mitotic activity. In addition, leukocyte common antigen was deposited in the extracellular matrix and on the cell membrane of target tumor cells. Pre-activated lymphocytes, in mixed cell cultures, failed to lyse the target tumor cells and underwent abnormal cell divisions, producing subsets similar to nuclear vlimata, which remained attached to the extracellular matrix. The morphological and immunocytochemical observations of lymphocytes were discussed and attributed to the presence of the specific extracellular matrix of glycosaminoglycans-proteasemembranes
Open Access
Matrix metalloproteinase-1 (MMP-1) and (MMP-8) gene polymorphisms promote increase and remodeling of the collagen III and V in posterior tibial tendinopathy
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Diniz Fernandes, Tulio; Godoy Santos, Alexandre Leme; Santos, Maria Cristina; Pontin, Pedro; Alves Pereira, Caio Augusto; Justi Jardim, Yuri; Pereira Velosa, Ana Paula; Maffulli, Nicola; Teodoro, Walcy Rosolia; Capelozzi, Vera Luiza
Posterior tibial tendinopathy (PTT) can lead to acquired flatfoot in adults. Many patients develop PTT without any identifiable risk factors. Molecular changes in extracellular matrix (ECM) and matrix metalloproteinase (MMP) polymorphism may influence the risk of developing PTT. We aim to investigate the association between matrix metalloproteinase-1 (MMP1) and (MMP-8) gene polymorphisms with changes in collagen I, III and V in PTT. A case-control study with 22 patients and 5 controls was performed. The MMP-1 (2G/2G) and MMP-8 (T/T) genotypes were determined by PCR-restriction fragment length polymorphism. Tendon specimens were evaluated by a histologic semiquantitative score, immunofluorescence and histomorphometry for collagen I, III and V. Tendon specimens from PTT demonstrated marked distortion of the architecture with necrosis, large basophilic areas with disruption of the normal linear orientation of collagen bundles, infiltration of inflammatory cells, dystrophic calcification and ossification. Under immunofluorescence, PTT tendon specimens showed weak green fluorescence and diffuse distribution of collagen I fibers, but strong fluorescence of collagen III and V. The collagen I fibers were significantly decreased whereas an increase of collagen III and V were found in PTT compared to control groups. In addition, PTT group presented a significant association with MMP-1 and MMP-8 gene polymorphisms. Patients with PTT matrix metalloproteinase-1 (MMP-1) and (MMP-8) gene polymorphisms presented an increase of the collagen III and V ratio, suggesting that the higher proportion in degenerated tendons could contribute to a decrease in the mechanical resistance of the tissue. Still, functional and association studies are needed to elucidate evident roles of MMPs in PTT.
Open Access
Mechanisms of neuroinflammation and inflammatory mediators involved in brain injury following subarachnoid hemorrhage
(Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Okada, Takeshi; Suzuki, Hidenori
Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular disorder. Neuro- inflammation is a critical cause of brain injury following SAH in both acute and chronic phases. While accumulating evidence has shown that therapies targeting neuroinflammation exerted beneficial effects in experimental SAH, there is little clinical evidence. One of the factors making neuroinflammation complicated is that inflammatory signaling pathways and mediators act as protective or detrimental responses at different phases. In addition, biomarkers to detect neuro- inflammation are little known in clinical settings. In this review, first, we discuss how the inflammatory signaling pathways contribute to brain injury and other secondary pathophysiological changes in SAH. Damage-associated molecular patterns arising from mechanical stress, transient global cerebral ischemia, red blood cell breakdown and delayed cerebral ischemia following SAH trigger to activate pattern recognition receptors (PRRs) such as Toll-like receptors, nucleotide-binding oligomerization domain-like receptors, and receptors for advanced glycation end products. Most of PRRs activate common downstream signaling transcriptional factor nuclear factor-κΒ and mitogen-activated protein kinases, releasing pro-inflammatory mediators and cytokines. Next, we focus on how pro-inflammatory substances play a role during the course of SAH. Finally, we highlight an important inducer of neuroinflammation, matricellular protein (MCP). MCPs are a component of extracellular matrix and exert beneficial and harmful effects through binding to receptors, other matrix proteins, growth factors, and cytokines. Treatment targeting MCPs is being proved efficacious in pre- clinical models for preventing brain injury including neuroinflammation in SAH. In addition, MCPs may be a candidate of biomarkers predicting brain injury following SAH in clinical settings.
Open Access
Prolonged oval cell proliferation with Ito cell activation and extracellular matrix accumulation in galactosamine-induced acute hepatitis in mini rats
(Murcia : F. Hernández, 1997) Uetsuka, K.; Suzuki, M.; Nakayama, Hiroyuki; Doi, K.
Histopathological and immunohistochemical studies were carried out on D-galactosamine (Ga1NAc)- induced acute hepatitis in rats of the JCl: Wistar TgN (ARGHGEN) 1 Nts strain (Mini rats), in which expression of the growth hormone gene is suppressed by an antisense transgene. Hepatitis characterized by hepatocellular acidophilic necrosis with inflammatory cell infiltration was most prominent at 2 days after GalNAc (1000mglkg)-injection, when proliferation of Ito cells and deposition of fibronectin and laminin were found along the sinusoidal linings. At 72 hours after GalNAc-injection, Ito cell proliferation with deposition of laminin and fibronectin became more prominent, and marked proliferation of small epithelial cells was observed in the periportal area. At 7 days after GalNAcinjection, quite a number of a-smooth muscle actinpositive Ito cells, surrounded by abundant fibronectin, laminin and type IV collagen, were still observed in close juxtaposition to rapidly proliferating small epithelial cells. The small epithelial cells were found to be positive for both a-fetoprotein and cytokeratin 7 and were therefore considered to be so-called oval cells. The results suggest that there may be some relation between oval cell proliferation, Ito cell activation and extracellular matrix accumulation in GalNAc-induced acute hepatitis in Mini rats.
Open Access
Regulation of tumor cell invasion by extracellular matrix
(Murcia : F. Hernández, 1999) Crowe, D.L.; Shuler, C.F.
The ability of malignant tumor cells to invade normal surrounding tissue contributes in large part to the significant morbidity and mortality of these cancers. The process of invasion involves adherence of the tumor cells to the extracellular matrix (ECM), degradation of matrix components, and movement of the cell body. Attachment to ECM molecules is mediated by the integrin family of extracellular matrix receptors. Integrins are a large family of heterodimeric proteins which transduce a variety of signals from the ECM. Ligand occupancy is critical for activation of integrin signaling. This signaling may occur via several different pathways. One of the best characterized of these pathways is the mitogen activated protein kinase (MAPK) cascade. This serial phosphorylation of substrate proteins terminates in activation of transcription factors which regulate expression of target genes. Many of these genes are critical for extracellular matrix degradation or cell migration. Among these are the matrix metalloproteinases (MMPs), a large family of ECM-degrading enzymes. Regulatory elements in the promoters of MMPs have been characterized, providing insight into how MMP expression is controlled. This review focuses on mechanisms by which the ECM regulates tumor cell invasion through integrin signaling via the MAPK pathway using MMP expression as the model.
Open Access
Role of extracellular matrix remodelling in adipose tissue pathophysiology. Relevance in the development of obesity
(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Frühbeck, Gema
Adipose tissue responds dynamically to alterations in nutrient excess through adipocyte hypertrophy and hyperplasia, followed by increased angiogenesis, immune cell infiltration, extracellular matrix (ECM) overproduction, and thus, increased production of proinflammatory adipokines during the progression of chronic inflammation. Adipose tissue remodelling is an ongoing process that is pathologically accelerated in the obese state in large part mediated by ECM proteins and proteases. The ECM is subject to major modifications by adipocytes and other cell types that are infiltrated in the adipose tissue, such as macrophages and vascular cells. In obesity, unusual expression of ECM components and fragments derived from tissue-remodelling processes can influence immune cell recruitment and activation, actively contributing to inflammation. ECM turnover requires a tightly regulated balance between the synthesis of the components and their proteolysis, mainly by fibrinolytic systems and matrix metalloproteases (MMPs). In this review, we discuss the key cellular steps that lead to adipose tissue remodelling and the main molecular mechanisms and mediators in this process. We highlight the importance of hypoxia and angiogenesis in the adipose remodelling process, as well as the cross-talk between adipocytes, macrophages and ECM components
Open Access
Schwann cell extracellular matrix molecules and their receptors
(Murcia : F. Hernández, 2000) Chernousov, M.A.; Carey, D.J.
The major cellular constituents of the mammalian peripheral nervous system are neurons (axons) and Schwann cells. During peripheral nerve development Schwann cells actively deposit extracellular matrix (ECM), comprised of basal lamina sheets that surround individual axon-Schwann cell units and collagen fibrils. These ECM structures are formed from a diverse set of macromolecules, consisting of glyco-proteins, collagens and proteoglycans. To,interact with ECM, Schwann cells express a number of integrin and non-integrin cell surface receptors. The expression of many Schwann cell ECM proteins and their receptors is developmentally regulated and, in some cases, dependent on axonal contact. Schwann cell ECM acts as an organizer of peripheral nerve tissue and strongly influences Schwann cell adhesion, growth and differentiation and regulates axonal growth during development and regeneration.
Open Access
Tenascin in the developing and adult human intestine
(Murcia : F. Hernández, 2000) Belanger, I.; Beaulieu, J.F.
The tenascins are a family of multifunctional extracellular matrix glycoproteins subject to complex spatial and temporal patterns of expression in the course of various organogenetic processes, namely those involving epithelial-mesenchymal interactions. In the intestine, the tenascins, in particular tenascin-C, have been found to be differentially expressed in the developing and adult small intestinal and colonic mucosa as well as in neoplasm. While tenascin-C emerges as a key player likely to be involved in intestinal mucosa development, maintenance and disease, its exact role in the regulation of fundamental intestinal cell function(s) such as proliferation, migration and tissue-specific gene expression remains however to be established.
Open Access
The matrix synthesis and anti-inflammatory effect of autologous leukocyte-poor platelet rich plasma in human cartilage explants
(Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Simental Mendía, Mario; Vilchez Cavazos, Félix; García Garza, Rubén; Lara Arias, Jorge; Montes de Oca Luna, Roberto; Said Fernández, Salvador; Martínez Rodríguez, Herminia G.
Objective. To determine the effects of autologous leukocyte-poor platelet-rich plasma (LPPRP) on the expression of markers involved in cartilageextracellular matrix production and inflammation in cartilage explants bearing osteoarthritis. Materials and Methods. Cartilage explants and LP-PRP were obtained from 10 patients who underwent total knee arthroplasty. The explants were cultured in spinner flasks for 28 days in the presence of interleukin (IL)-1β and/or LP-PRP. The gene expression of catabolic (MMP13, ADAMTS5, and IL1β) and anabolic factors (COL2A1, ACAN, and SOX9) was quantified. A histological assessment was performed according to a modified Mankin score, and quantification of type II and I collagen deposition. Results. The gene expression of catabolic factors and the Mankin score were lower in LP-PRP- and LP-PRP/IL1β- than in IL-1β-treated explants, suggesting less matrix degradation in explants cultured in the presence of LP-PRP. Higher expression of genes involved in cartilage matrix restoration was observed in LP-PRP and LP-PRP/IL-1β- when compared to IL-1β-treated explants. The explants treated with LP-PRP and LPPRP/IL-1β exhibited a higher deposition of type II collagen as well as a lower deposition of type I collagen and also better surface integrity and a significant increase in the number of chondrocytes. Conclusion. LPPRP treatment favored restoration in early osteoarthritic cartilage and reduced the pro-inflammatory effect of IL1β. LP-PRP is a promising therapy for early osteoarthritis, as it promotes extracellular matrix repair, reduces inflammation, and slows cartilage degeneration.
Open Access
Thrombospondin-1 expression in breast cancer: prognostic significance and association with p53 alterations, tumour angiogenesis and extracellular matrix components
(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2012) Ioachim, E.; Damala, K.; Tsanou, E.; Briasoulis, E.; Papadiotis, E.; Mitselou, Antigony; Charchanti, A.; Doukas, M.; Lampri, L.; Arvanitis, D.L.
Thrombospondin (TSP-1) is a 450-kd adhesive glycoprotein that was initially discovered in platelets and subsequently in a variety of cell types. Several reports suggest that TSP-1 possesses tumour suppressor function, through its ability to inhibit tumour neovascularization. In this study we investigated tissue sections from 124 breast carcinomas for the immuno-histochemical expression of TSP-1 protein and its relationship to several clinicopathological parameters. The possible relationship to hormone receptors content, p53 protein, proliferation associated indices, angiogenesis, VEGF expression and extracellular matrix components (tenascin, fibronectin, laminin, collagen type IV and syndecan-1) was also estimated. TSP-1 was detected in the perivascular tissue, at the epithelial-stromal junction, in the stroma and in the tumour cells. High tumour cell TSP-1 expression was observed in 9.7%, moderate in 17.7%, mild in 10.5%, while 62.1% of the cases were negative for TSP-1 expression. The survival analysis showed an increased risk of recurrence associated with low TSP-1 tumour cell expression. High stromal TSP-1 expression was observed in 3.2% of the cases, moderate in 3.3%, mild in 27.4%, while 63.6% of the cases showed absence of TSP-1 expression. This expression was higher in invasive lobular type of breast cancer and inversely correlated with the lymph node involvement and the estrogen receptor content. Stromal TSP-1 expression was also positively correlated with extracellular matrix components expression, tenascin, fibronectin, collagen type IV, laminin, and syndecan-1. The relationship of TSP-1 expression with tumor angiogenesis, growth fraction and p53 protein expression was not significant. Our data suggest that TSP-1 expression seems to be associated with favorable biological behavior and may have clinical value in terms of predicting the risk of recurrence. In addition, TSP-1 might not be a direct anti-angiogenic factor, although it seems to be implicated in the remodeling of breast cancer tissue through interaction with other extracellular matrix components

Browsing by Subject "Extracellular matrix"

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