scholarly journals Linking Oxidative Stress and DNA Damage to Changes in the Expression of Extracellular Matrix Components

2021 ◽  
Vol 12 ◽  
Author(s):  
Susana G. Martins ◽  
Rita Zilhão ◽  
Sólveig Thorsteinsdóttir ◽  
Ana Rita Carlos
Keyword(s):  
Oxidative Stress ◽  
Extracellular Matrix ◽  
Dna Damage ◽  
Uv Light ◽  
Tissue Homeostasis ◽  
Strong Impact ◽  
Ecm Remodeling ◽  
Extracellular Matrix Components ◽  
Genes Encoding ◽  
Negative Impacts

Cells are subjected to endogenous [e.g., reactive oxygen species (ROS), replication stress] and exogenous insults (e.g., UV light, ionizing radiation, and certain chemicals), which can affect the synthesis and/or stability of different macromolecules required for cell and tissue function. Oxidative stress, caused by excess ROS, and DNA damage, triggered in response to different sources, are countered and resolved by specific mechanisms, allowing the normal physiological equilibrium of cells and tissues to be restored. One process that is affected by oxidative stress and DNA damage is extracellular matrix (ECM) remodeling, which is a continuous and highly controlled mechanism that allows tissues to readjust in reaction to different challenges. The crosstalk between oxidative stress/DNA damage and ECM remodeling is not unidirectional. Quite on the contrary, mutations in ECM genes have a strong impact on tissue homeostasis and are characterized by increased oxidative stress and potentially also accumulation of DNA damage. In this review, we will discuss how oxidative stress and DNA damage affect the expression and deposition of ECM molecules and conversely how mutations in genes encoding ECM components trigger accumulation of oxidative stress and DNA damage. Both situations hamper the reestablishment of cell and tissue homeostasis, with negative impacts on tissue and organ function, which can be a driver for severe pathological conditions.

scholarly journals Cancer Cell-derived Secretory Factors in Breast Cancer-associated Lung Metastasis: Their Mechanism and Future Prospects

2020 ◽  
Vol 20 (3) ◽  
pp. 168-186 ◽  
Author(s):  
Tabinda Urooj ◽  
Bushra Wasim ◽  
Shamim Mushtaq ◽  
Syed Nudrat Nawaid Shah ◽  
Muzna Shah
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Cancer Cell ◽  
Lung Metastasis ◽  
Primary Site ◽  
Ecm Remodeling ◽  
Metastatic Cells ◽  
Extracellular Matrix Components ◽  
Matrix Components

: In Breast cancer, Lung is the second most common site of metastasis after the bone. Various factors are responsible for Lung metastasis occurring secondary to Breast cancer. Cancer cellderived secretory factors are commonly known as ‘Cancer Secretomes’. They exhibit a prompt role in the mechanism of Breast cancer lung metastasis. They are also major constituents of hostassociated tumor microenvironment. Through cross-talk between cancer cells and the extracellular matrix components, cancer cell-derived extracellular matrix components (CCECs) such as hyaluronan, collagens, laminin and fibronectin cause ECM remodeling at the primary site (breast) of cancer. However, at the secondary site (lung), tenascin C, periostin and lysyl oxidase, along with pro-metastatic molecules Coco and GALNT14, contribute to the formation of pre-metastatic niche (PMN) by promoting ECM remodeling and lung metastatic cells colonization. Cancer cell-derived secretory factors by inducing cancer cell proliferation at the primary site, their invasion through the tissues and vessels and early colonization of metastatic cells in the PMN, potentiate the mechanism of Lung metastasis in Breast cancer. : On the basis of biochemical structure, these secretory factors are broadly classified into proteins and non-proteins. This is the first review that has highlighted the role of cancer cell-derived secretory factors in Breast cancer Lung metastasis (BCLM). It also enumerates various researches that have been conducted to date in breast cancer cell lines and animal models that depict the prompt role of various types of cancer cell-derived secretory factors involved in the process of Breast cancer lung metastasis. In the future, by therapeutically targeting these cancer driven molecules, this specific type of organ-tropic metastasis in breast cancer can be successfully treated.

scholarly journals The Diagnostic Usefulness of Circulating Profile of Extracellular Matrix Components: Sulfated Glycosaminoglycans (sGAG), Hyaluronan (HA) and Extracellular Part of Syndecan-1 (sCD138) in Patients with Crohn’s Disease and Ulcerative Colitis

2021 ◽  
Vol 10 (8) ◽  
pp. 1722
Author(s):  
Alicja Derkacz ◽  
Paweł Olczyk ◽  
Agnieszka Jura-Półtorak ◽  
Krystyna Olczyk ◽  
Katarzyna Komosinska-Vassev
Keyword(s):  
Ulcerative Colitis ◽  
Extracellular Matrix ◽  
Ecm Remodeling ◽  
Mayo Score ◽  
Extracellular Matrix Components ◽  
Adalimumab Therapy ◽  
Bowel Diseases ◽  
Diagnostic Usefulness ◽  
Quantitative Changes ◽  
One Year

The described research focused on the diagnostic usefulness of sulfated glycosaminoglycans (sGAG), hyaluronan (HA), and extracellular part of syndecan-1 (sCD138) as new markers related to extracellular matrix (ECM) remodeling in the intestine during the two most common forms of inflammatory bowel diseases (IBD), i.e., ulcerative colitis (UC) and Crohn’ disease (CD). Inflammatory markers belonging to ECM components were assessed in serum of patients with IBD using an immunoenzymatic method (HA and sCD138) and a method based on the reaction with dimethylmethylene blue (sulfated GAG). Measurements were carried out twice: at baseline and after one year of therapy with prednisone (patients with CD) or adalimumab (patients with UC). No quantitative changes were observed in serum sGAG, HA, and sCD138 concentrations between patients newly diagnosed with CD and the healthy group. In the case of patients with UC, the parameter which significantly differentiated healthy subjects and patients with IBD before biological therapy was HA. Significant correlation between serum HA level and inflammation activity, expressed as Mayo score, was also observed in patients with UC. Moreover, the obtained results have confirmed that steroid therapy with prednisone significantly influenced the circulating profile of all examined ECM components (sGAG, HA, and sCD138), whereas adalimumab therapy in patients with UC led to a significant change in only circulating sGAG levels. Moreover, the significant differences in serum HA levels between patients with UC and CD indicate that quantification of circulating HA may be useful in the differential diagnosis of CD and UC.

scholarly journals Healthy Subcutaneous and Omental Adipose Tissue Is Associated with High Expression of Extracellular Matrix Components

2022 ◽  
Vol 23 (1) ◽  
pp. 520
Author(s):  
Matúš Soták ◽  
Meenu Rohini Rajan ◽  
Madison Clark ◽  
Christina Biörserud ◽  
Ville Wallenius ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Adipose Tissue ◽  
Lysyl Oxidase ◽  
Subcutaneous Fat ◽  
High Expression ◽  
Adipose Tissues ◽  
Ecm Remodeling ◽  
Omental Adipose Tissue ◽  
Extracellular Matrix Components ◽  
Metabolic Conditions

Obesity is associated with extensive expansion and remodeling of the adipose tissue architecture, including its microenvironment and extracellular matrix (ECM). Although obesity has been reported to induce adipose tissue fibrosis, the composition of the ECM under healthy physiological conditions has remained underexplored and debated. Here, we used a combination of three established techniques (picrosirius red staining, a colorimetric hydroxyproline assay, and sensitive gene expression measurements) to evaluate the status of the ECM in metabolically healthy lean (MHL) and metabolically unhealthy obese (MUO) subjects. We investigated ECM deposition in the two major human adipose tissues, namely the omental and subcutaneous depots. Biopsies were obtained from the same anatomic region of respective individuals. We found robust ECM deposition in MHL subjects, which correlated with high expression of collagens and enzymes involved in ECM remodeling. In contrast, MUO individuals showed lower expression of ECM components but elevated levels of ECM cross-linking and adhesion proteins, e.g., lysyl oxidase and thrombospondin. Our data suggests that subcutaneous fat is more prone to express proteins involved in ECM remodeling than omental adipose tissues. We conclude that a more dynamic ability to deposit and remodel ECM may be a key signature of healthy adipose tissue, and that subcutaneous fat may adapt more readily to changing metabolic conditions than omental fat.

scholarly journals Tert-Butylhydroquinone Prevents Oxidative Stress-Mediated Apoptosis and Extracellular Matrix Degradation in Rat Chondrocytes

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Bo Yang ◽  
Haisheng Huang ◽  
Qisong He ◽  
Wei Lu ◽  
Lu Zheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Extracellular Matrix ◽  
Matrix Metalloproteinase ◽  
Protein Expression ◽  
Cell Viability ◽  
Cell Counting ◽  
Expression Levels ◽  
Extracellular Matrix Components ◽  
Mrna And Protein Expression

Oxidative stress-induced chondrocyte apoptosis and degradation of the extracellular matrix (ECM) play an important role in the progression of osteoarthritis (OA). In addition, tert-butylhydroquinone (TBHQ) is an activator of the nuclear factor erythroid derived-2-related factor 2 (Nrf2). The present study aimed to determine the effectiveness of TBHQ in preventing the apoptosis of chondrocytes and degradation of the extracellular matrix, induced by oxidative stress, in vitro. Therefore, rat chondrocytes were exposed to 20 μM tert-butyl hydroperoxide (TBHP) for 24 h to establish an oxidative damage model, in vitro. Thereafter, cell viability was evaluated using the Cell Counting Kit-8 assay. Moreover, the level of ROS was determined through 2′,7′-dichlorofluorescein diacetate staining. The mitochondrial membrane potential of chondrocytes was also measured using JC-1. Furthermore, cell apoptosis was assessed through Annexin V-fluorescein isothiocyanate/propidium iodide staining. The study also performed Western blotting and qPCR to evaluate the expression of extracellular matrix components, matrix catabolic enzymes, and changes in signalling pathways. The results showed that 2.5 and 5 μM of TBHQ reduced the TBHP-induced generation of excessive ROS and improved cell viability. Additionally, 2.5 and 5 μM of TBHQ prevented mitochondrial damage and apoptosis in rat chondrocytes. Treatment with TBHQ also increased the mRNA and protein expression levels of aggrecan and collagen II. However, TBHQ reduced the mRNA and protein expression levels of matrix metalloproteinase 3 (MMP3) and matrix metalloproteinase 13 (MMP13) in rat chondrocytes. In addition, treatment with TBHQ enhanced the protein expression levels of Nrf2, NADPH quinone oxidoreductase 1 (NQO-1), and hemeoxygenase-1 (HO-1) in rat chondrocytes. The current study showed that TBHQ was not only effective in protecting against TBHP-induced oxidative stress but also inhibited the apoptosis of rat chondrocytes and degradation of the ECM by activating the Nrf2 pathway. The results therefore suggest that TBHQ holds potential for use in the treatment of OA.

scholarly journals The Role of Extracellular Matrix Components in Inflammatory Bowel Diseases

2021 ◽  
Vol 10 (5) ◽  
pp. 1122
Author(s):  
Alicja Derkacz ◽  
Paweł Olczyk ◽  
Krystyna Olczyk ◽  
Katarzyna Komosinska-Vassev
Keyword(s):  
Extracellular Matrix ◽  
Inflammatory Bowel Diseases ◽  
Healing Process ◽  
Immunological Response ◽  
Matrix Remodeling ◽  
Ecm Remodeling ◽  
Intestinal Fibrosis ◽  
Extracellular Matrix Components ◽  
Bowel Diseases ◽  
Inflammatory Bowel

The remodeling of extracellular matrix (ECM) within the intestine tissues, which simultaneously involves an increased degradation of ECM components and excessive intestinal fibrosis, is a defining trait of the progression of inflammatory bowel diseases (IBDs), which include ulcerative colitis (UC) and Crohn’s disease (CD). The increased activity of proteases, especially matrix metalloproteinases (MMPs), leads to excessive degradation of the extracellular matrix and the release of protein and glycoprotein fragments, previously joined with the extracellular matrix, into the circulation. MMPs participate in regulating the functions of the epithelial barrier, the immunological response, and the process of wound healing or intestinal fibrosis. At a later stage of fibrosis during IBD, excessive formation and deposition of the matrix is observed. To assess changes in the extracellular matrix, quantitative measurement of the concentration in the blood of markers dependent on the activity of proteases, involved in the breakdown of extracellular matrix proteins as well as markers indicating the formation of a new ECM, has recently been proposed. This paper describes attempts to use the quantification of ECM components as markers to predict intestinal fibrosis and evaluate the healing process of the gut. The markers which reflect increased ECM degradation, together with the ones which show the process of creating a new matrix during IBD, allow the attainment of important information regarding the changes in the intestinal tissue, epithelial integrity and extracellular matrix remodeling. This paper contains evidence confirming that ECM remodeling is an integral part of directional cell signaling in the progression of IBD, and not only a basis for the ongoing processes.

scholarly journals Matrix Metalloproteinases and Arterial Hypertension: Role of Oxidative Stress and Nitric Oxide in Vascular Functional and Structural Alterations

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 585
Author(s):  
Alejandro F. Prado ◽  
Rose I. M. Batista ◽  
Jose E. Tanus-Santos ◽  
Raquel F. Gerlach
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Extracellular Matrix ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Protective Effects ◽  
Pathophysiological Mechanisms ◽  
Emerging Therapies ◽  
Extracellular Matrix Components ◽  
Matrix Components

Various pathophysiological mechanisms have been implicated in hypertension, but those resulting in vascular dysfunction and remodeling are critical and may help to identify critical pharmacological targets. This mini-review article focuses on central mechanisms contributing to the vascular dysfunction and remodeling of hypertension, increased oxidative stress and impaired nitric oxide (NO) bioavailability, which enhance vascular matrix metalloproteinase (MMP) activity. The relationship between NO, MMP and oxidative stress culminating in the vascular alterations of hypertension is examined. While the alterations of hypertension are not fully attributable to these pathophysiological mechanisms, there is strong evidence that such mechanisms play critical roles in increasing vascular MMP expression and activity, thus resulting in abnormal degradation of extracellular matrix components, receptors, peptides, and intracellular proteins involved in the regulation of vascular function and structure. Imbalanced vascular MMP activity promotes vasoconstriction and impairs vasodilation, stimulating vascular smooth muscle cells (VSMC) to switch from contractile to synthetic phenotypes, thus facilitating cell growth or migration, which is associated with the deposition of extracellular matrix components. Finally, the protective effects of MMP inhibitors, antioxidants and drugs that enhance vascular NO activity are briefly discussed. Newly emerging therapies that address these essential mechanisms may offer significant advantages to prevent vascular remodeling in hypertensive patients.

scholarly journals Immunoexpression of metalloproteinases 9 (MMP-9) and 2 (MMP-2) and their inhibitors (TIMP-1 and TIMP-2) in normal and neoplastic canine mammary tissue

2020 ◽  
Vol 21 ◽  
Author(s):  
Hugo Henrique Ferreira ◽  
Denise Caroline Toledo ◽  
Adriana Marques Faria ◽  
Diego Pereira Araújo ◽  
Andrigo Barboza di Nardi ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Epithelial Cells ◽  
Stromal Cells ◽  
Normal Breast ◽  
Tissue Homeostasis ◽  
Favorable Condition ◽  
Mammary Tissue ◽  
Tumor Evolution ◽  
Ecm Remodeling ◽  
Positive Correlation

Abstract The aim of this study was to perform the immunostaining of MMP-9 and MMP-2 and its inhibitors, TIMP-1 and TIMP-2, on normal and neoplastic canine mammary tissue in order to evaluate the behavior of these proteins in extracellular matrix (ECM) remodeling in different neoplastic mammary types. Thus, 48 samples of canine mammary tissue were analyzed, 14 of which complex carcinomas, 13 tubulopapillary carcinomas, six single adenomas and 15 normal mammary tissue. There were differences in MMP-9, TIMP-1 and TIMP-2 according to mammary histomorphology, and MMP-9 presented increased immunoexpression in epithelial and stromal cells in tubulopapillary and complex carcinomas. TIMP-1 exhibited reduced immunostaining in the stromal cells of the complex carcinomas and TIMP-2 enhanced immunostaining in the epithelial cells of tubulopapillary carcinomas. There was a positive correlation between MMP-9 and TIMP-1 in epithelial and stromal cells regarding immunostaining intensity and number of labeled cells in the normal breast. There was a positive correlation between MMP-9 and TIMP-2 in the epithelial cells of tubulopapillary carcinomas. It is concluded that balanced activity between MMP-9, MMP-2, TIMP-1 and TIMP-2 maintains normal canine mammary tissue homeostasis while increased immunoexpression of MMP-9 and TIMP-2 and reduced TIMP- 1 in carcinomas suggest a favorable condition for tumor evolution.

scholarly journals Link between increased cellular senescence and extracellular matrix changes in COPD

2020 ◽  
Vol 319 (1) ◽  
pp. L48-L60 ◽  
Author(s):  
Roy R. Woldhuis ◽  
Maaike de Vries ◽  
Wim Timens ◽  
Maarten van den Berge ◽  
Marco Demaria ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Extracellular Matrix ◽  
Dna Damage ◽  
Lung Tissue ◽  
Cellular Senescence ◽  
Accelerated Aging ◽  
Lung Fibroblasts ◽  
Copd Patients ◽  
And Oxidative Stress ◽  
P16 Expression

Chronic obstructive pulmonary disease (COPD) is associated with features of accelerated aging, including cellular senescence, DNA damage, oxidative stress, and extracellular matrix (ECM) changes. We propose that these features are particularly apparent in patients with severe, early-onset (SEO)-COPD. Whether fibroblasts from COPD patients display features of accelerated aging and whether this is also present in relatively young SEO-COPD patients is unknown. Therefore, we aimed to determine markers of aging in (SEO)-COPD-derived lung fibroblasts and investigate the impact on ECM. Aging hallmarks and ECM markers were analyzed in lung fibroblasts from SEO-COPD and older COPD patients and compared with fibroblasts from matched non-COPD groups ( n = 9–11 per group), both at normal culture conditions and upon Paraquat-induced senescence. COPD-related differences in senescence and ECM expression were validated in lung tissue. Higher levels of cellular senescence, including senescence-associated β-galactosidase (SA-β-gal)-positive cells (19% for COPD vs. 13% for control) and p16 expression, DNA damage (γ-H2A.X-positive nuclei), and oxidative stress ( MGST1) were detected in COPD compared with control-derived fibroblasts. Most effects were also different in SEO-COPD, with SA-β-gal-positive cells only being significant in SEO-COPD vs. matched controls. Lower decorin expression in COPD-derived fibroblasts correlated with higher p16 expression, and this association was confirmed in lung tissue. Paraquat treatment induced cellular senescence along with clear changes in ECM expression, including decorin. Fibroblasts from COPD patients, including SEO-COPD, display higher levels of cellular senescence, DNA damage, and oxidative stress. The association between cellular senescence and ECM expression changes may suggest a link between accelerated aging and ECM dysregulation in COPD.

scholarly journals Syndecan-4-/- mice have smaller muscle fibers, increased Akt/mTOR/S6K1 and Notch/HES-1 pathways, and alterations in extracellular matrix components

2020 ◽  
Author(s):  
Sissel Beate Rønning ◽  
Cathrine Rein Carlson ◽  
Jan Magnus Aronsen ◽  
Addolorata Pisconti ◽  
Vibeke Høst ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Protein Level ◽  
Cell Activation ◽  
Molecular Mechanisms ◽  
Muscle Development ◽  
Muscle Fibers ◽  
Mrna Levels ◽  
Ecm Remodeling ◽  
Genetic Ablation ◽  
Extracellular Matrix Components

AbstractBackgroundExtracellular matrix (ECM) remodeling is essential for skeletal muscle development and adaption in response to environmental cues such as exercise and injury. The cell surface proteoglycan syndecan-4 has been reported to be essential for muscle differentiation, but few molecular mechanisms are known. Syndecan-4-/- mice are unable to regenerate damaged muscle, and display deficient satellite cell activation, proliferation, and differentiation. A reduced myofiber basal lamina has also been reported in syndecan-4-/- muscle, indicating possible defects in ECM production. To get a better understanding of the underlying molecular mechanisms, we have here investigated the effects of syndecan-4 genetic ablation on molecules involved in ECM remodeling and muscle growth, both under steady state conditions and in response to exercise.MethodsTibialis anterior (TA) muscles from sedentary and exercised syndecan-4-/- and WT mice were analyzed by immunohistochemistry, real-time PCR and western blotting.ResultsCompared to WT, we found that syndecan-4-/- mice had reduced body weight, reduced muscle weight, muscle fibers with a smaller cross-sectional area, and reduced expression of myogenic regulatory transcription factors. Sedentary syndecan-4-/- had also increased mRNA levels of syndecan-2, decorin, collagens, fibromodulin, biglycan, and LOX. Some of these latter ECM components were reduced at protein level, suggesting them to be more susceptible to degradation or less efficiently translated when syndecan-4 is absent. At the protein level, TRPC7 was reduced, whereas activation of the Akt/mTOR/S6K1 and Notch/HES-1 pathways were increased. Finally, although exercise induced upregulation of several of these components in WT, a further upregulation of these molecules was not observed in exercised syndecan-4-/- mice.ConclusionsAltogether our data suggest an important role of syndecan-4 in muscle development.

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