scholarly journals Matrix Metalloproteinase 13 Activity is Required for Normal and Hypoxia-Induced Precocious Hatching in Zebrafish Embryos

2020 ◽  
Vol 8 (1) ◽  
pp. 3
Author(s):  
Christopher D. Small ◽  
Megan el-Khoury ◽  
Ghislain Deslongchamps ◽  
Tillmann J. Benfey ◽  
Bryan D. Crawford
Keyword(s):  
Matrix Metalloproteinase ◽  
Environmental Conditions ◽  
Molecular Mechanisms ◽  
Zebrafish Embryos ◽  
Clear Understanding ◽  
Hatching Enzyme ◽  
Pharmacological Inhibition ◽  
Matrix Metalloproteinase 13 ◽  
Hatching Gland

Hypoxia induces precocious hatching in zebrafish, but we do not have a clear understanding of the molecular mechanisms regulating the activation of the hatching enzyme or how these mechanisms trigger precocious hatching under unfavorable environmental conditions. Using immunohistochemistry, pharmacological inhibition of matrix metalloproteinase 13 (Mmp13), and in vivo zymography, we show that Mmp13a is present in the hatching gland just as embryos become hatching competent and that Mmp13a activity is required for both normal hatching and hypoxia-induced precocious hatching. We conclude that Mmp13a likely functions in activating the hatching enzyme zymogen and that Mmp13a activity is necessary but not sufficient for hatching in zebrafish. This study highlights the broad nature of MMP function in development and provides a non-mammalian example of extra-embryonic processes mediated by MMP activity.

scholarly journals Antioxidant, Anti-Inflammatory and Anti-Angiogenic Properties of Citrus lumia Juice

2020 ◽  
Vol 11 ◽  
Author(s):  
Antonella Smeriglio ◽  
Marcella Denaro ◽  
Valeria D’Angelo ◽  
Maria Paola Germanò ◽  
Domenico Trombetta
Keyword(s):  
Ascorbic Acid ◽  
Acid Content ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Ascorbic Acid Content ◽  
Zebrafish Embryos ◽  
Anti Inflammatory ◽  
Dose Dependent

Citrus juices are a rich source of bioactive compounds with various and well-known health benefits. The aim of this study was to investigate the polyphenols and ascorbic acid content as well as to investigate the antioxidant, anti-inflammatory and anti-angiogenic properties of the juice of an ancient Mediterranean species, Citrus lumia Risso (CLJ). The antioxidant and anti-inflammatory activities were evaluated by several in vitro cell-free and cell-based assays, whereas two different in vivo models, the chick chorioallantoic membrane (CAM) and the zebrafish embryos, were used to characterize the anti-angiogenic properties. Twenty-eight polyphenols were identified by RP-LC-DAD-ESI-MS analysis (flavonoids 68.82% and phenolic acids 31.18%) with 1-caffeoyl-5-feruloylquinic acid and kaempferol 3′-rhamnoside, which represent the most abundant compounds (25.70 and 23.12%, respectively). HPLC-DAD analysis showed a high ascorbic acid content (352 mg/kg of CLJ), which contributes with polyphenols to the marked and dose-dependent antioxidant and anti-inflammatory properties observed. CLJ showed strong and dose-dependent anti-angiogenic activity as highlighted by the inhibition of blood vessel formation on CAMs and the decrease of endogenous alkaline phosphatase on zebrafish embryos. Moreover, within the concentration range tested, no dead or malformed embryos were recorded. Certainly, further studies are needed to investigate the molecular mechanisms underlying these promising biological effects, but considering the evidence of the present study, the use of CLJ as a ready-to drink safe prevention strategy for inflammatory-based diseases correlated to angiogenesis could be justified.

scholarly journals In Vivo Interstitial Migration of Primitive Macrophages Mediated by JNK-Matrix Metalloproteinase 13 Signaling in Response to Acute Injury

2008 ◽  
Vol 181 (3) ◽  
pp. 2155-2164 ◽  
Author(s):  
Yong Zhang ◽  
Xue-Tao Bai ◽  
Kang-Yong Zhu ◽  
Yi Jin ◽  
Min Deng ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Acute Injury ◽  
Matrix Metalloproteinase 13

Silencing matrix metalloproteinase-13 (Mmp-13) reduces inflammatory bone resorption associated with LPS-induced periodontal disease in vivo

2020 ◽  
Author(s):  
Morgana R. Guimaraes-Stabili ◽  
Marcell Costa de Medeiros ◽  
Danuza Rossi ◽  
Angelo Constantino Camilli ◽  
Cleslei Fernando Zanelli ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Matrix Metalloproteinase ◽  
Periodontal Disease ◽  
Matrix Metalloproteinase 13

Parathyroid hormone increases the expression level of matrix metalloproteinase-13 in vivo

2001 ◽  
Vol 19 (4) ◽  
pp. 207-212 ◽  
Author(s):  
Motoyuki Uchida ◽  
Hideyuki Yamato ◽  
Yumiko Nagai ◽  
Hiroshi Yamagiwa ◽  
Tadashi Hayami ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Matrix Metalloproteinase ◽  
Expression Level ◽  
Matrix Metalloproteinase 13

scholarly journals Radiolabeled Selective Matrix Metalloproteinase 13 (MMP-13) Inhibitors: (Radio)Syntheses and in Vitro and First in Vivo Evaluation

2016 ◽  
Vol 60 (1) ◽  
pp. 307-321 ◽  
Author(s):  
Verena Hugenberg ◽  
Stefan Wagner ◽  
Klaus Kopka ◽  
Michael Schäfers ◽  
Robert C. Schuit ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
In Vivo Evaluation ◽  
Matrix Metalloproteinase 13

scholarly journals Small Molecule Screening in Zebrafish Embryos Identifies Signaling Pathways Regulating Early Thyroid Development

2019 ◽  
Author(s):  
Benoit Haerlingen ◽  
Robert Opitz ◽  
Isabelle Vandernoot ◽  
Achim Trubiroha ◽  
Pierre Gillotay ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Small Molecule ◽  
Molecular Mechanisms ◽  
Model Organisms ◽  
Thyroid Cell ◽  
Zebrafish Embryos ◽  
Cardiovascular Development ◽  
Drug Induced ◽  
Thyroid Development

AbstractBackgroundDefects in embryonic development of the thyroid gland are a major cause for congenital hypothyroidism in human newborns but the underlying molecular mechanisms are still poorly understood. Organ development relies on a tightly regulated interplay between extrinsic signaling cues and cell intrinsic factors. At present, however, there is limited knowledge about the specific extrinsic signaling cues that regulate foregut endoderm patterning, thyroid cell specification and subsequent morphogenetic processes in thyroid development.MethodsTo begin to address this problem in a systematic way, we used zebrafish embryos to perform a series of in vivo phenotype-driven chemical genetic screens to identify signaling cues regulating early thyroid development. For this purpose, we treated zebrafish embryos during different developmental periods with a panel of small molecule compounds known to manipulate the activity of major signaling pathways and scored phenotypic deviations in thyroid, endoderm and cardiovascular development using whole mount in situ hybridization and transgenic fluorescent reporter models.ResultsSystematic assessment of drugged embryos recovered a range of thyroid phenotypes including expansion, reduction or lack of the early thyroid anlage, defective thyroid budding as well as hypoplastic, enlarged or overtly disorganized presentation of the thyroid primordium after budding. Our pharmacological screening identified BMP and FGF signaling as key factors for thyroid specification and early thyroid organogenesis, highlight the importance of low Wnt activities during early development for thyroid specification and implicate drug-induced cardiac and vascular anomalies as likely indirect mechanisms causing various forms of thyroid dysgenesis.ConclusionsBy integrating the outcome of our screening efforts with previously available information from other model organisms including Xenopus, chicken and mouse, we conclude that signaling cues regulating thyroid development appear broadly conserved across vertebrates. We therefore expect that observations made in zebrafish can inform mammalian models of thyroid organogenesis to further our understanding of the molecular mechanisms of congenital thyroid diseases.

Abstract 311: Inhibition Of Matrix Metalloproteinase-13 Dependent Protease-activated Receptor-1 Activation Attenuates Fibrotic Signaling

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Allison E Dixon ◽  
Fabrice Jaffre ◽  
Nigel Mackman ◽  
Burns C Blaxall
Keyword(s):  
Matrix Metalloproteinase ◽  
Cardiac Remodeling ◽  
Cardiac Fibroblasts ◽  
The United States ◽  
Matrix Metalloproteinase 13 ◽  
Ecm Proteins ◽  
Excess Production ◽  
Potential Therapeutic Role ◽  
Protease Activated Receptor 1

Heart failure (HF) is the leading cause of morbidity and mortality in the United States and is characterized by progressive myocardial fibrosis, pathologic remodeling and deteriorating cardiac function. Cardiac fibroblasts (CF) are largely responsible for the secretion of ECM proteins as well as cytokines and growth factors in the heart. Upon injury or pathologic stimulation, CF transition to a myofibroblast phenotype, leading to excess production of ECM proteins and pro-inflammatory cytokines. Previous studies in our lab have indicated a role for protease-activated receptor-1 (PAR-1), the most highly expressed GPCR on CF, in pathologic cardiac remodeling. In particular, we reported the novel cleavage of PAR-1 via matrix metalloproteinase-13 (MMP-13) and cardioprotective effects of MMP-13 inhibition in an acute model of HF. Therefore, we hypothesize that MMP-13 plays an important role in cardiac remodeling through activation of PAR-1, particularly in the pathologic transition of CF to myofibroblasts. To investigate this hypothesis, RNA was collected from hearts of mice infused with isoproterenol (ISO) for 7 days and concurrently treated with a specific MMP-13 inhibitor, WAY170523, or vehicle. To evaluate the effect of WAY170523, we used qRT-PCR to measure changes in the expression of fibrotic markers, COL1a1, COL3a1, and TGF-β. Inhibition of MMP-13 with WAY170523 attenuated expression of these genes compared to vehicle treated animals. We previously reported that stimulation of CF and cardiomyocytes with MMP-13 induces phosphorylation of ERK1/2, a member of the MAPK family known to play a role in cardiac hypertrophy, and treatment with a direct PAR-1 antagonist decreased the activation of ERK1/2. We have found that ERK1/2 phosphorylation is directly attenuated following inhibition of MMP-13 with WAY170523. Overall, these data suggest a role for MMP-13 dependent PAR-1 activation in pathologic myofibroblast transition and a potential therapeutic role for MMP-13 inhibition, possibly through its inhibition of ERK1/2 phosphorylation. Treatment with WAY170523 also attenuates markers of fibrosis in vivo, indicating a potential salutary role for MMP-13 inhibition in the treatment of HF.

Overexpression of Runx2 directed by the matrix metalloproteinase-13 promoter containing the AP-1 and Runx/RD/Cbfa sites alters bone remodeling in vivo

2006 ◽  
Vol 99 (2) ◽  
pp. 545-557 ◽  
Author(s):  
Nagarajan Selvamurugan ◽  
Stephen C. Jefcoat ◽  
Sukyee Kwok ◽  
Rodney Kowalewski ◽  
Joseph A. Tamasi ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Bone Remodeling ◽  
Matrix Metalloproteinase 13 ◽  
The Matrix

Role of iNOS and peroxynitrite–matrix metalloproteinase-2 signaling in myocardial late preconditioning in rats

2010 ◽  
Vol 299 (2) ◽  
pp. H512-H518 ◽  
Author(s):  
Péter Bencsik ◽  
Krisztina Kupai ◽  
Zoltán Giricz ◽  
Anikó Görbe ◽  
Judit Pipis ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Infarct Size ◽  
Coronary Occlusion ◽  
Matrix Metalloproteinase 2 ◽  
No Production ◽  
Causative Role ◽  
Inos Activity ◽  
Pharmacological Inhibition

We have previously shown that the inhibition of myocardial nitric oxide (NO) and peroxynitrite-matrix metalloproteinase (MMP) signaling by early preconditioning (PC) is involved in its cardioprotective effect. Therefore, in the present study, we investigated the role of NO and peroxynitrite-MMP signaling in the development of late PC. PC was performed by five consecutive cycles of 4-min coronary occlusion and 4-min reperfusion in anesthetized rats in vivo. Twenty-four hours later, hearts were subjected to a 30-min coronary occlusion followed by 180-min reperfusion to measure infarct size. In separate experiments, heart tissue was sampled to measure biochemical parameters before and 3, 6, 12, or 24 h after the PC protocol, respectively. Late PC decreased infarct size, increased cardiac inducible NO synthase (iNOS) activity and gene expression, and decreased SOD activity at 24 h significantly compared with sham-operated controls. Late PC increased cardiac superoxide levels significantly at 24 h; however, it did not change cardiac NO levels. Cardiac peroxynitrite levels were significantly decreased. Downstream cellular targets of peroxynitrite, MMP-2 and MMP-9 activities were decreased in the late PC group at 24 h compared with the sham-operated group. To verify if PC-induced inhibition of MMPs had a causative role in the reduction of infarct size, in separate experiments, we measured infarct size after the pharmacological inhibition of MMPs by ilomastat and found a significant reduction of infarct size compared with the vehicle-treated group. In conclusion, this is the first demonstration that the inhibition of cardiac peroxynitrite-MMP signaling contributes to cardioprotection by late PC and that pharmacological inhibition of MMPs is able to reduce infarct size in vivo. Furthermore, increased expression of iNOS may play a role in the development of late PC; however, increased iNOS activity does not lead to increased NO production in late PC.

scholarly journals Galectin network in osteoarthritis: galectin-4 programs a pathogenic signature of gene and effector expression in human chondrocytes in vitro

2021 ◽  
Author(s):  
Katharina M. Pichler ◽  
Anita Fischer ◽  
Jürgen Alphonsus ◽  
Catharina Chiari ◽  
Sebastian Schmidt ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Cartilage Degradation ◽  
Cross Linking ◽  
Transcriptome Data ◽  
Matrix Metalloproteinase 13 ◽  
Carbohydrate Recognition Domains ◽  
Inflammatory Proteins ◽  
Oa Chondrocytes

AbstractGalectin-4 (Gal-4) is a member of the galectin family, which have been identified as galactose-binding proteins. Gal-4 possesses two tandem repeat carbohydrate recognition domains and acts as a cross-linking bridge in sulfatide-dependent glycoprotein routing. We herein document its upregulation in osteoarthritis (OA) in correlation with the extent of cartilage degradation in vivo. Primary human OA chondrocytes in vitro respond to carbohydrate-inhibitable Gal-4 binding with the upregulation of pro-degradative/-inflammatory proteins such as interleukin-1β (IL-1β) and matrix metalloproteinase-13 (MMP-13), as documented by RT-qPCR-based mRNA profiling and transcriptome data processing. Activation of p65 by phosphorylation of Ser536 within the NF-κB pathway and the effect of three p65 inhibitors on Gal-4 activity support downstream involvement of such signaling. In 3D (pellet) cultures, Gal-4 presence causes morphological and biochemical signs of degradation. Taken together, our findings strongly support the concept of galectins acting as a network in OA pathogenesis and suggest that blocking their activity in disease progression may become clinically relevant in the future.

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