scholarly journals The Versatile Role of Matrix Metalloproteinase for the Diverse Results of Fibrosis Treatment

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4188 ◽  
Author(s):  
Hong-Meng Chuang ◽  
Yu-Shuan Chen ◽  
Horng-Jyh Harn
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Cardiovascular Diseases ◽  
De Novo ◽  
Biological Processes ◽  
Tissue Formation ◽  
Ecm Degradation ◽  
Excessive Secretion ◽  
Wound Tissue

Fibrosis is a type of chronic organ failure, resulting in the excessive secretion of extracellular matrix (ECM). ECM protects wound tissue from infection and additional injury, and is gradually degraded during wound healing. For some unknown reasons, myofibroblasts (the cells that secrete ECM) do not undergo apoptosis; this is associated with the continuous secretion of ECM and reduced ECM degradation even during de novo tissue formation. Thus, matrix metalloproteinases (MMPs) are considered to be a potential target of fibrosis treatment because they are the main groups of ECM-degrading enzymes. However, MMPs participate not only in ECM degradation but also in the development of various biological processes that show the potential to treat diseases such as stroke, cardiovascular diseases, and arthritis. Therefore, treatment involving the targeting of MMPs might impede typical functions. Here, we evaluated the links between these MMP functions and possible detrimental effects of fibrosis treatment, and also considered possible approaches for further applications.

Regulation of hyaluronan synthesis by vasodilatory prostaglandins

2007 ◽  
Vol 98 (08) ◽  
pp. 287-295 ◽  
Author(s):  
Karsten Schrör ◽  
Jens Fischer
Keyword(s):  
Extracellular Matrix ◽  
Wound Healing ◽  
Plasma Membrane ◽  
Receptor Subtypes ◽  
Biological Processes ◽  
Vascular Remodelling ◽  
Malignant Growth ◽  
Prostaglandin Receptor ◽  
Structural Functions

SummaryHyaluronan (HA) is a macromolecular polysaccharide of the vascular extracellular matrix that confers both structural functions as well as signalling activity. HA is involved in a wide variety of biological processes, such as tissue morphogenesis, malignant growth and metastasis, wound healing and angiogenesis. In atherosclerosis, HA associates with leukocytes and vascular smooth muscle cells (VSMC) and is involved in vascular remodelling. HA is synthesized at the plasma membrane by three HAsynthase isoforms (HAS1–3). Human VSMC upregulate HAS1 and HAS2 in response to prostaglandins via Gs-coupled prostaglandin receptor subtypes IP and EP2. This review discusses the regulation of HA-synthesis by prostaglandins and the evidence for a central role of cyclooxygenase-2/PGE2 in regulation of HAsynthesis during atherogenesis.

scholarly journals Extracellular Matrix Optimization for Enhanced Physiological Relevance in Hepatic Tissue-Chips

Polymers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 3016
Author(s):  
Abdul Rahim Chethikkattuveli Salih ◽  
Kinam Hyun ◽  
Arun Asif ◽  
Afaque Manzoor Soomro ◽  
Hafiz Muhammad Umer Farooqi ◽  
...  
Keyword(s):  
Image Processing ◽  
Extracellular Matrix ◽  
Drug Screening ◽  
Human Liver ◽  
Growth Patterns ◽  
Surface Coatings ◽  
Hepatic Tissue ◽  
Tissue Formation ◽  
Tissue Development

The cellular microenvironment is influenced explicitly by the extracellular matrix (ECM), the main tissue support biomaterial, as a decisive factor for tissue growth patterns. The recent emergence of hepatic microphysiological systems (MPS) provide the basic physiological emulation of the human liver for drug screening. However, engineering microfluidic devices with standardized surface coatings of ECM may improve MPS-based organ-specific emulation for improved drug screening. The influence of surface coatings of different ECM types on tissue development needs to be optimized. Additionally, an intensity-based image processing tool and transepithelial electrical resistance (TEER) sensor may assist in the analysis of tissue formation capacity under the influence of different ECM types. The current study highlights the role of ECM coatings for improved tissue formation, implying the additional role of image processing and TEER sensors. We studied hepatic tissue formation under the influence of multiple concentrations of Matrigel, collagen, fibronectin, and poly-L-lysine. Based on experimental data, a mathematical model was developed, and ECM concentrations were validated for better tissue development. TEER sensor and image processing data were used to evaluate the development of a hepatic MPS for human liver physiology modeling. Image analysis data for tissue formation was further strengthened by metabolic quantification of albumin, urea, and cytochrome P450. Standardized ECM type for MPS may improve clinical relevance for modeling hepatic tissue microenvironment, and image processing possibly enhance the tissue analysis of the MPS.

Modeling Cell-Cell Adhesion With a Cadherin Based Model

2012 ◽  
Author(s):  
John Dallon
Keyword(s):  
Wound Healing ◽  
Cell Adhesion ◽  
Tissue Formation ◽  
Adhesion Sites ◽  
Actin Structure ◽  
Cell Cell

Cell-cell adhesion is critical in morphogenesis, tissue formation, cancer, and wound healing. A better understanding of cell-cell adhesion mediated by cadherins will allow all these processes to be mimicked and manipulated to achieve desired objectives. This paper investigates the role of the actin structure associated with cadherin adhesion sites.

scholarly journals LncRNA XIST promotes extracellular matrix synthesis, proliferation and migration by targeting miR-29b-3p/COL1A1 in human skin fibroblasts after thermal injury

2019 ◽  
Vol 52 (1) ◽  
Author(s):  
Wei Cao ◽  
Youping Feng
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Wound Healing ◽  
Western Blot ◽  
Thermal Injury ◽  
Human Skin Fibroblasts ◽  
Cell Proliferation And Migration ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background Long noncoding RNAs (lncRNAs) have been reported to be associated with dermis process during burn wound healing. This study aimed to investigate the role of lncRNA X-inactive specific transcript (XIST) in human skin fibroblasts (HSF) and extracellular matrix (ECM) as well as the regulatory network of XIST/microRNA-29b-3p (miR-29b-3p)/collagen 1 alpha 1 (COL1A1). Methods The wound samples were collected from 25 patients with deep partial thickness burn at day 5 after burn. The thermal injured model was established using HSF cells. The expressions of XIST, miR-29b-3p and COL1A1 were measured by quantitative real-time polymerase chain reaction and western blot. ECM synthesis, cell proliferation and migration were detected by western blot, cell counting kit-8 and trans-well assays, respectively. The interaction between miR-29b-3p and XIST or COL1A1 was explored by bioinformatics analysis and luciferase reporter assay. Results The expressions of XIST and COL1A1 were enhanced but miR-29b-3p expression was decreased after thermal injury. XIST overexpression promoted ECM synthesis, cell proliferation and migration in thermal injured HSF cells. However, XIST knockdown played an opposite effect. miR-29b-3p overexpression inhibited ECM synthesis, cell proliferation and migration, which was reversed by XIST. COL1A1 silence suppressed ECM synthesis, cell proliferation and migration by miR-29b-3p targeting. Moreover, COL1A1 up-regulation weakened the effect of XIST silence on ECM synthesis and HSF cell function. Conclusion XIST promoted ECM synthesis, cell proliferation and migration by sponging miR-29b-3p and targeting COL1A1 in HSF cells after thermal injury, indicating the promoting role of XIST in wound healing.

scholarly journals De novo morphogenesis of testis tissue: an improved bioassay to investigate the role of VEGF165 during testis formation

Reproduction ◽  
2014 ◽  
Vol 148 (1) ◽  
pp. 109-117 ◽  
Author(s):  
Camila Dores ◽  
Ina Dobrinski
Keyword(s):  
Blood Vessel ◽  
Cell Suspension ◽  
Germ Cells ◽  
De Novo ◽  
Donor Cell ◽  
Seminiferous Tubules ◽  
Tissue Formation ◽  
Tubule Formation ◽  
Testis Tissue

De novo formation of testis tissue from single-cell suspensions allows manipulation of different testicular compartments before grafting to study testicular development and the spermatogonial stem cell niche. However, the low percentages of newly formed seminiferous tubules supporting complete spermatogenesis and lack of a defined protocol have limited the use of this bioassay. Low spermatogenic efficiency in de novo formed tissue could result from the scarcity of germ cells in the donor cell suspension, cell damage caused by handling or from hypoxia during tissue formation in the host environment. In this study, we compared different proportions of spermatogonia in the donor cell suspension and the use of Matrigel as a scaffold to support de novo tissue formation and spermatogenesis. Then, we used the system to investigate the role of vascular endothelial growth factor 165 (VEGF165) during testicular morphogenesis on blood vessel and seminiferous tubule formation, and on presence of germ cells in the de novo developed tubules. Our results show that donor cell pellets with 10×106 porcine neonatal testicular cells in Matrigel efficiently formed testis tissue de novo. Contrary to what was expected, the enrichment of the cell suspension with germ cells did not result in higher numbers of tubules supporting spermatogenesis. The addition of VEGF165 did not improve blood vessel or tubule formation, but it enhanced the number of tubules containing spermatogonia. These results indicate that spermatogenic efficiency was improved by the addition of Matrigel, and that VEGF165 may have a protective role supporting germ cell establishment in their niche.

scholarly journals Extracellular matrix endocytosis in controlling matrix turnover and beyond: emerging roles in cancer

2016 ◽  
Vol 44 (5) ◽  
pp. 1347-1354 ◽  
Author(s):  
Elena Rainero
Keyword(s):  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Secreted Proteins ◽  
Oncogenic Transformation ◽  
Intracellular Degradation ◽  
Cell Functions ◽  
Ecm Degradation

The extracellular matrix (ECM) is a network of secreted proteins that, beyond providing support for tissues and organs, is involved in the regulation of a variety of cell functions, including cell proliferation, polarity, migration and oncogenic transformation. ECM homeostasis is maintained through a tightly controlled balance between synthesis, deposition and degradation. While the role of metalloproteases in ECM degradation is widely recognised, the contribution of ECM internalisation and intracellular degradation to ECM maintenance has been mostly overlooked. In this review, I will summarise what is known about the molecular mechanisms mediating ECM endocytosis and how this process impacts on diseases, such as fibrosis and cancer.

Role of plasmin and gelatinase in extracellular matrix degradation by cultured rat mesangial cells

1992 ◽  
Vol 263 (6) ◽  
pp. F1112-F1118 ◽  
Author(s):  
A. P. Wong ◽  
S. L. Cortez ◽  
W. H. Baricos
Keyword(s):  
Extracellular Matrix ◽  
Mesangial Cells ◽  
Cell Number ◽  
Plasmin Activity ◽  
High Positive Correlation ◽  
Gelatinase Activity ◽  
Inactive Form ◽  
Ecm Degradation ◽  
Plasmin Inhibitors

We have examined the ability of mesangial cells (MCs) to degrade extracellular matrix (ECM) using cultured rat MCs grown on thin films of radiolabeled Matrigel. ECM degradation by cultured MCs was observed only in presence of exogenously added plasminogen and was a function of plasminogen concentration (0-50 mU), cell number (0-50,000 cells), and length of incubation (0-72 h). A high positive correlation (r > 0.93) was observed between ECM degradation and plasmin activity in medium, suggesting an important role for plasmin in ECM degradation by cultured MCs. This suggestion was confirmed by ability of plasmin inhibitors, alpha 2-antiplasmin (40 micrograms/ml) and aprotinin (216 kallikrein inhibition units/ml), to inhibit (> 90%) ECM degradation. Inhibitors of cysteine proteinases [trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane, 10 microM] and aspartic proteinases (pepstatin, 5.0 micrograms/ml) had no effect on ECM degradation. However, in presence of plasminogen, inhibitors of matrix metalloproteinases, TIMP-1 (40 micrograms/ml) and o-phenanthroline (100 microM), inhibited ECM degradation -42 +/- 4% and -43 +/- 3% (SE), respectively (n = 8-10). Thus, in addition to plasmin, a matrix metalloproteinase(s) is also involved in ECM degradation by cultured rat MCs. Zymography of culture medium obtained from MCs grown on radiolabeled Matrigel films in absence of plasminogen revealed only two closely migrating bands of gelatinase activity, relative mol wt of approximately 70,000-72,000. MCs grown in absence of plasminogen failed to degrade ECM despite presence of gelatinase in medium, indicating that, in absence of plasmin, gelatinase is present in an inactive form, either as a latent proenzyme or as a gelatinase-inhibitor complex.(ABSTRACT TRUNCATED AT 250 WORDS)

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