scholarly journals Dynamic Expression of Membrane Type 1-Matrix Metalloproteinase (Mt1-mmp/Mmp14) in the Mouse Embryo

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2448
Author(s):  
Emma Muñoz-Sáez ◽  
Natalia Moracho ◽  
Ana I. R. Learte ◽  
Alicia G. Arroyo ◽  
Cristina Sánchez-Camacho
Keyword(s):  
Transmembrane Domain ◽  
Vascular System ◽  
System Development ◽  
Immunohistochemical Analysis ◽  
Cardiovascular Development ◽  
Lacz Reporter ◽  
Spatiotemporal Expression ◽  
Dynamic Expression ◽  
The Matrix ◽  
Membrane Type

MT1-MMP/MMP14 belongs to a subgroup of the matrix metalloproteinases family that presents a transmembrane domain, with a cytosolic tail and the catalytic site exposed to the extracellular space. Deficient mice for this enzyme result in early postnatal death and display severe defects in skeletal, muscle and lung development. By using a transgenic line expressing the LacZ reporter under the control of the endogenous Mt1-mmp promoter, we reported a dynamic spatiotemporal expression pattern for Mt1-mmp from early embryonic to perinatal stages during cardiovascular development and brain formation. Thus, Mt1-mmp shows expression in the endocardium of the heart and the truncus arteriosus by E8.5, and is also strongly detected during vascular system development as well as in endothelial cells. In the brain, LacZ reporter expression was detected in the olfactory bulb, the rostral cerebral cortex and the caudal mesencephalic tectum. LacZ-positive cells were observed in neural progenitors of the spinal cord, neural crest cells and the intersomitic region. In the limb, Mt1-mmp expression was restricted to blood vessels, cartilage primordium and muscles. Detection of the enzyme was confirmed by Western blot and immunohistochemical analysis. We suggest novel functions for this metalloproteinase in angiogenesis, endocardial formation and vascularization during organogenesis. Moreover, Mt1-mmp expression revealed that the enzyme may contribute to heart, muscle and brain throughout development.

scholarly journals In vivo evidence for the unique kinetics of evoked dopamine release in the patch and matrix compartments of the striatum

2021 ◽  
Author(s):  
Andrea Jaquins-Gerstl ◽  
Kathryn M. Nesbitt ◽  
Adrian C. Michael
Keyword(s):  
Dopamine Release ◽  
Spatial Organization ◽  
Dorsal Striatum ◽  
Immunohistochemical Analysis ◽  
Extensive Literature ◽  
Fast Scan Cyclic Voltammetry ◽  
Medial Dorsal ◽  
The Matrix ◽  
Slow Kinetic

AbstractThe neurochemical transmitter dopamine (DA) is implicated in a number of diseases states, including Parkinson’s disease, schizophrenia, and drug abuse. DA terminal fields in the dorsal striatum and core region of the nucleus accumbens in the rat brain are organized as heterogeneous domains exhibiting fast and slow kinetic of DA release. The rates of dopamine release are significantly and substantially faster in the fast domains relative to the slow domains. The striatum is composed of a mosaic of spatial compartments known as the striosomes (patches) and the matrix. Extensive literature exists on the spatial organization of the patch and matrix compartments and their functions. However, little is known about these compartments as they relate to fast and slow kinetic DA domains observed by fast scan cyclic voltammetry (FSCV). Thus, we combined high spatial resolution of FSCV with detailed immunohistochemical analysis of these architectural compartments (patch and matrix) using fluorescence microscopy. Our findings demonstrated a direct correlation between patch compartments with fast domain DA kinetics and matrix compartments to slow domain DA kinetics. We also investigated the kinetic domains in two very distinct sub-regions in the striatum, the lateral dorsal striatum (LDS) and the medial dorsal striatum (MDS). The lateral dorsal striatum as opposed to the medial dorsal striatum is mainly governed by fast kinetic DA domains. These finding are highly relevant as they may hold key promise in unraveling the fast and slow kinetic DA domains and their physiological significance. Graphical abstract

Gene Trap, Gene Knockout, Gene Knock-In, and Transgenics in Vascular Development

1999 ◽  
Vol 82 (08) ◽  
pp. 865-869 ◽  
Author(s):  
Thomas Sato
Keyword(s):  
Animal Models ◽  
Molecular Mechanisms ◽  
Vascular System ◽  
System Development ◽  
Gene Knockout ◽  
Vascular Development ◽  
Branching Morphogenesis ◽  
Abnormal Development ◽  
Organ Systems ◽  
Almost All

IntroductionThe vascular system is one of the first organ systems to develop in our bodies. Normal development and maturation of the physiological functions of almost all of the other organs are critically dependent on the accurate and tightly controlled establishment of the vascular system. Our understanding of the mechanisms underlying the formation of the vascular system during development is still in its infancy. With further understanding of these mechanisms, we may eventually be able to correct the abnormal development and the malfunctioning of many organs by therapeutically modulating the morphology and/or physiological function of the vascular system.Our further understanding of the vascular development can, in part, be achieved by discovering the molecules that play critical roles in this process. We could also achieve this goal by learning more about the functions of previously identified molecules in the vascular system. Discovery of new processes underlying the development of the vascular system will also contribute to further understanding of these molecular mechanisms.Recent advances, using the whole genome approach, have resulted in a flood of new information. This trend will continue, and fortunately, a number of molecular reagents will become available. Therefore, the field will likely experience an exponential growth in terms of novel biological insights and discovering the mechanisms of vascular system development.Occasionally, reductionistic approaches help to systematically address a number of biological problems, including the problems associated with vascular system development. One such approach is to choose an organism that allows us to systematically address these biological questions. The choice of animal models that are well-suited for the study of a particular question has led to a large number of discoveries. To address questions in vascular system development, current research has focused on animal models, including fish, frog, bird, and mouse, and also studies involving humans. It is also worthwhile to note that the branching morphogenesis of the fly trachea system has been utilized to address fundamental questions of vascular morphogenesis.This chapter will summarize the genomic manipulation of the murine vascular system to address questions regarding vascular development. In addition, the advances that have been made in this field using such methods will be summarized.

Expression patterns and immunohistochemical analysis of ERK, HRAS and MEK1 proteins during ovarian prehierarchical follicular development in Zi geese (Anser cygnoides)

2019 ◽  
Author(s):  
H. Lu ◽  
C. T. Sello ◽  
C. Liu ◽  
Y. Sui ◽  
C. Xu ◽  
...  
Keyword(s):  
Protein Localization ◽  
Quantitative Polymerase Chain Reaction ◽  
Expression Patterns ◽  
Follicular Development ◽  
Immunohistochemical Analysis ◽  
Mitogen Activated Protein Kinase ◽  
Expression Levels ◽  
Protein Levels ◽  
Spatiotemporal Expression ◽  
Mitogen Activated Protein

The objective of this study was to investigate the spatiotemporal expression levels and protein localization of extracellular regulated MAP kinase (ERK), HRas proto-oncogene, GTPase (HRAS), and mitogen-activated protein kinase kinase 1 (MEK1) genes in ovarian prehierarchical follicles of geese. The prehierarchical follicles from healthy laying geese (n=6) at the age of 35 to 37 weeks were harvested. The relative expression levels of ERK, HRAS, and MEK1 in various sized prehierarchical follicles were detected by real-time quantitative polymerase chain reaction (RT-qPCR), western blotting, and follicular wall localization was investigated by using immunohistochemistry. The results revealed that the candidate genes were expressed differently at mRNA and protein levels at five stages of prehierarchical follicle development. These results suggest that ERK, HRAS, and MEK1 might be associated to the key biological mechanisms regulating Zi geese folliculogenesis.

scholarly journals From Blood Islands to Blood Vessels: Morphologic Observations and Expression of Key Molecules during Hyaloid Vascular System Development

2012 ◽  
Vol 53 (13) ◽  
pp. 7912 ◽  
Author(s):  
D. Scott McLeod ◽  
Takuya Hasegawa ◽  
Takayuki Baba ◽  
Rhonda Grebe ◽  
Ines Galtier d'Auriac ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Vascular System ◽  
System Development

scholarly journals FINANCIAL SYSTEM DEVELOPMENT IN REPUBLIC OF MOLDOVA IN THE CONTEXT OF THE NEW INTERNATIONAL FINANCIAL ARCHITECTURE

World Science ◽  
2019 ◽  
Vol 2 (10(50)) ◽  
pp. 4-9
Author(s):  
Lopotenco Viorica
Keyword(s):  
Structural Changes ◽  
System Development ◽  
Financial System ◽  
Matrix Approach ◽  
Financial Architecture ◽  
Republic Of Moldova ◽  
International Financial Architecture ◽  
The Matrix ◽  
Structured Approach ◽  
General Preferences

The primary purpose of this paper is to analyze the transformations in the international financial architecture and their impact on the national financial system. For this purpose, a multi-criteria analysis (matrix approach) is used, which represents a structured approach used to determine the general preferences between several alternative options, which lead to the achievement of several objectives. The approach of the matrix gives the possibility to combine the size of the set of the financial sector.The conclusions of this study consist in the fact that the complex resolution of the challenges in the international financial architecture implies the creation of foundations for the implementation of the progressive structural changes in the economy, capable of contributing to the sustainable economic development.

scholarly journals Cardiac remodeling and MMPs on the model of chronic daunorubicin-induced cardiomyopathy in rabbits

2010 ◽  
pp. 831-836
Author(s):  
M Adamcová ◽  
A Potáčová ◽  
O Popelová ◽  
M Štěrba ◽  
Y Mazurová ◽  
...  
Keyword(s):  
Cardiac Remodeling ◽  
Biochemical Analysis ◽  
Interstitial Fibrosis ◽  
Morphological Changes ◽  
Immunohistochemical Analysis ◽  
Treated Group ◽  
Insoluble Fraction ◽  
Anthracycline Cardiotoxicity ◽  
Myocardial Interstitial Fibrosis ◽  
The Matrix

The matrix metalloproteinases (MMPs) play a key role during cardiac remodeling. The aim of the study was to investigate the changes in collagenous proteins and MMPs in the model of non-ischemic, anthracycline-induced chronic cardiomyopathy in rabbits using both biochemical and histological approaches. The study was carried out in three groups of Chinchilla male rabbits: 1) daunorubicin (3 mg/kg, once weekly for 10 weeks), 2) control (saline in the same schedule), 3) daunorubicin with the cardioprotectant dexrazoxane (60 mg/kg, before each daunorubicin). Morphological changes in the myocardium of daunorubicin-treated animals were characterized by focal myocardial interstitial fibrosis of different intensity. The subsequent proliferation of the fibrotic tissue was marked by an increased content of both collagen types I and III, which resulted in their typical coexpression in the majority of bundles of fibers forming either smaller or larger scars. Biochemical analysis showed a significantly increased concentration of hydroxyproline, mainly in the pepsin-insoluble fraction of collagenous proteins, in the daunorubicin-treated group (1.42±0.12 mg/g) as compared with the control (1.03±0.04 mg/g) and dexrazoxane (1.07±0.07 mg/g) groups. Dexrazoxane co-administration remarkably reduced the cardiotoxic effects of daunorubicin to the extent comparable with the controls in all evaluated parameters. Using zymography, it was possible to detect only a gelatinolytic band corresponding to MMP-2 (MMP-9 activity was not detectable). However, no significant changes in MMP-2 activity were determined between individual groups. Immunohistochemical analysis revealed increased MMP-2 expression in both cardiomyocytes and fibroblasts. Thus, this study has revealed specific alterations in the collagen network in chronic anthracycline cardiotoxicity in relationship to the expression and activity of major MMPs.

scholarly journals Discovery of Therapeutic Candidates for Diabetic Retinopathy Based on Molecular Switch Analysis: Application of a Systematic Process

2022 ◽  
Vol 2022 ◽  
pp. 1-20
Author(s):  
Yue Ren ◽  
Yanan Liu ◽  
Kaiyang Liu ◽  
Xiaoqian Huo ◽  
Chaoqun Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Vascular System ◽  
System Development ◽  
Molecular Switch ◽  
Stress Injury ◽  
Systematic Process ◽  
Oxidative Stress Injury ◽  
Pathogenic Factors ◽  
Nrf2 Signaling Pathway

The pathogenesis of diabetic retinopathy (DR) is complicated, and there is no effective drug. Oxidative stress-induced human retinal microvascular endothelial cells (HRMECs) injury is one of the pathogenic factors for DR. Molecular switches are considered high-risk targets in disease progression. Identification of molecular switch is crucial to interpret the pathogenesis of disease and screen effective ingredients. In this study, a systematic process was executed to discover therapeutic candidates for DR based on HRMECs injury. First of all, the molecular mechanism of HRMECs oxidative stress injury was revealed by transcriptomics and network pharmacology. We found that oxidative stress was one of the pivotal pathogenic factors, which interfered with vascular system development, inflammation, cell adhesion, and cytoskeleton damaged HRMECs through crosstalk. Then, network topology analysis was used to recognize molecular switches. The results indicated that the Keap1-Nrf2-ARE signaling pathway was the molecular switch in HRMECs oxidative stress injury. On this basis, the HEK293-ARE overexpression cell line was applied to obtain 18 active traditional Chinese medicine (TCM) ingredients. Furthermore, andrographolide, one of the 18 candidates, was applied in the HRMECs oxidative stress model to evaluate the accuracy of the systematic process. The efficacy evaluation results showed that andrographolide could regulate oxidative stress, vascular system development, inflammation, adhesion, and skeleton tissue to inhibit HRMECs injury cooperatively. And its mechanism was related to the Nrf2 signaling pathway. Overall, our data suggest that the Nrf2 signaling pathway is the molecular switch in the HRMECs oxidative stress injury. 18 potential Nrf2 agonists are likely to be promising DR candidates.

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