The gelatinases, matrix metalloproteinases 2 and 9, play individual roles in skeleton development
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE223750 | GEO | 2023/03/07
REPOSITORIES: GEO
Similar Datasets
Project description:Extracellular matrix (ECM) assembly/disassembly is a critical regulator for airway epithelial development and remodeling. Airway organoid is widely used in respiratory research, yet there is limited study to indicate the roles and mechanismsof ECM organization in epithelial growth and differentiation by using in vitro organoid system. Moreover, most of current Matrigel-based airway organoids are in basal-out orientation where accessing the apical surface is challenging. We present a novel human apical-out airway organoid using a biochemically defined hybrid hydrogel system. During human nasal epithelial progenitor cells (hNEPCs) differentiation, thegel gradually degraded, leading to the organoid apical surfaces facing outward. The expression and activity of ECM-degrading enzymes, matrix metalloproteinases (MMP7, MMP9, MMP10 and MMP13) increased during organoid differentiation,where inhibition of MMPs significantly suppressed the normal ciliation, resulting in increased goblet cell proportion. Moreover, a decrease of MMPs was found in goblet cell hyperplastic epithelium in inflammatory mucosa. This system reveals essential roles of epithelial-derived MMPs on epithelial cell fate determination, and provides an applicable platform enabling further study for ECM in regulating airway development in health and diseases.
2023-12-11 | GSE249160 | GEO
Project description:This is the model described in the article:
A biochemical model of matrix metalloproteinase 9 activation and inhibition.
Vempati P, Karagiannis ED, Popel AS. J Biol Chem.
2007 Dec 28;282(52):37585-96. Pubmed ID: 17848556
,
doi: 10.1074/jbc.M611500200
.
Abstract:
Matrix metalloproteinases (MMPs) are a class of extracellular and membrane-bound proteases involved in an array of physiological processes, including angiogenesis. We present a detailed computational model of MMP9 activation and inhibition. Our model is validated to existing biochemical experimental data. We determine kinetic rate constants for the processes of MMP9 activation by MMP3, MMP10, MMP13, and trypsin; inhibition by the tissue inhibitors of metalloproteinases (TIMPs) 1 and 2; and MMP9 deactivation. This computational approach allows us to investigate discrepancies in our understanding of the interaction of MMP9 with TIMP1. Specifically, we find that inhibition due to a single binding event cannot describe MMP9 inhibition by TIMP1. Temporally accurate biphasic inhibition requires either an additional isomerization step or a second lower affinity isoform of MMP9. We also theoretically characterize the MMP3/TIMP2/pro-MMP9 and MMP3/TIMP1/pro-MMP9 systems. We speculate that these systems differ significantly in their time scales of activation and inhibition such that MMP9 is able to temporarily overshoot its final equilibrium value in the latter. Our numerical simulations suggest that the ability of pro-MMP9 to complex TIMP1 increases this overshoot. In all, our analysis serves as a summary of existing kinetic data for MMP9 and a foundation for future models utilizing MMP9 or other MMPs under physiologically well defined microenvironments.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model is:
Vempati, Karagiannis, Popel, 2007 version 1
The original CellML model was created and curated by:
Catherine May Lloyd
c.lloyd(at)auckland.ac.nz
The University of Auckland, Bioengineering Institute
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
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In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL7888000034 | BioModels
Project description:The process of tumor invasion requires degradation of extracellular matrix by proteolytic enzymes. Cancer cells form protrusive invadopodia, which produce and release matrix metalloproteinases (MMPs) to degrade the basement membrane and thereby allowing metastasis. We investigated the effect of LASP1, a newly identified protein in invadopodia, on expression, secretion and activation of MMPs in invasive breast tumor cells. By analyzing and verifying microarray data sets and performing reporter assays, we demonstrate that LASP1 positively modulates the expression of c-Fos and AP-1 activity, and thereby up-regulates expression of MMP1, -3 and -9 in breast cancer cells. Furthermore, zymography assays and Western blot analysis revealed cytosolic LASP1 promotion of MMP vesicle secretion into the extracellular matrix, thus altering the microenvironment during cancer progression. The newly identified role of LASP1 in regulating matrix degradation by affecting MMP transcription and secretion elucidated the migratory potential observed in studies that investigated the upregulation of LASP1 in aggressive cancers.
2017-02-03 | GSE77584 | GEO
Project description:HIV1+ smokers develop emphysema at an earlier age and with a higher incidence than HIV1- smokers. Based on the knowledge that human alveolar macrophages (AM) are capable of producing proteases that degrade extracellular matrix components, we hypothesized that upregulation of AM matrix metalloproteinases may be associated with the emphysema of HIV1+ smokers. To test this hypothesis, microarray analysis was used to screen which MMP genes were expressed by AM isolated by bronchoalveolar lavage (BAL) of HIV1+ smokers with early emphysema. For each of the MMP genes observed to be expressed (MMP-1, -2, -7, -9, -10, -12 and -14), TaqMan PCR was used to quantify the relative expression in AM from 4 groups of individuals: HIV1 healthy nonsmokers, HIV1- healthy smokers, HIV1- smokers with early emphysema and HIV1+ smokers with early emphysema. Strikingly, while AM gene expression of MMPs was higher in HIV1- individuals with emphysema in comparison with HIV1- healthy smokers, for the majority of the MMPs (-1, -7, -9, -10, -12), AM expression from HIV1+ smokers with early emphysema was significantly higher than HIV1- smokers with early emphysema. Consistent with these observations, HIV1+ individuals with early emphysema had higher levels of epithelial lining fluid MMPs (-2, -7, -9,-12) than the 3 HIV1 groups. Interestingly, the active forms of MMP-2, -9 and -12 were detected in epithelial lining fluid from HIV1+ individuals with early emphysema, but not in any of the other groups. Considering that the substrate specificity of the upregulated AM MMPs includes collagenases, gelatinases, matrilysins and elastase, these data suggest that upregulated AM MMP genes and activation of MMP proteins may contribute to the emphysema of HIV1+ individuals who smoke. Keywords: expression study Asymptomatic HIV+ smokers with early emphysema
2016-03-24 | E-GEOD-10038 | biostudies-arrayexpress
Project description:Osteoclasts are multinucleated, bone-resorbing cells. However, they also digest cartilage during skeletal maintenance, development and in degradative conditions including osteoarthritis, rheumatoid arthritis and primary bone sarcoma. This study explores the mechanisms behind the osteoclast–cartilage interaction. Human osteoclasts differentiated on acellular human cartilage expressed osteoclast marker genes (e.g. CTSK, MMP9) and proteins (TRAP, VNR), visibly damaged the cartilage surface and released glycosaminoglycan in a contact-dependent manner. Direct co-culture with chondrocytes during differentiation increased large osteoclast formation (p < 0.0001) except when co-cultured on dentine, when osteoclast formation was inhibited (p = 0.0002). Osteoclasts cultured on dentine inhibited basal cartilage degradation (p = 0.012). RNA-seq identified MMP8 overexpression in osteoclasts differentiated on cartilage versus dentine (8.89-fold, p = 0.0133), while MMP9 was the most highly expressed MMP. Both MMP8 and MMP9 were produced by osteoclasts in osteosarcoma tissue. This study suggests that bone-resident osteoclasts and chondrocytes exert mutually protective effects on their ‘native’ tissue. However, when osteoclasts contact non-native cartilage they cause degradation via MMPs. Understanding the role of osteoclasts in cartilage maintenance and degradation might identify new therapeutic approaches for pathologies characterized by cartilage degeneration.
2021-12-01 | GSE166535 | GEO
Project description:HIV1+ smokers develop emphysema at an earlier age and with a higher incidence than HIV1- smokers. Based on the knowledge that human alveolar macrophages (AM) are capable of producing proteases that degrade extracellular matrix components, we hypothesized that upregulation of AM matrix metalloproteinases may be associated with the emphysema of HIV1+ smokers. To test this hypothesis, microarray analysis was used to screen which MMP genes were expressed by AM isolated by bronchoalveolar lavage (BAL) of HIV1+ smokers with early emphysema. For each of the MMP genes observed to be expressed (MMP-1, -2, -7, -9, -10, -12 and -14), TaqMan PCR was used to quantify the relative expression in AM from 4 groups of individuals: HIV1 healthy nonsmokers, HIV1- healthy smokers, HIV1- smokers with early emphysema and HIV1+ smokers with early emphysema. Strikingly, while AM gene expression of MMPs was higher in HIV1- individuals with emphysema in comparison with HIV1- healthy smokers, for the majority of the MMPs (-1, -7, -9, -10, -12), AM expression from HIV1+ smokers with early emphysema was significantly higher than HIV1- smokers with early emphysema. Consistent with these observations, HIV1+ individuals with early emphysema had higher levels of epithelial lining fluid MMPs (-2, -7, -9,-12) than the 3 HIV1 groups. Interestingly, the active forms of MMP-2, -9 and -12 were detected in epithelial lining fluid from HIV1+ individuals with early emphysema, but not in any of the other groups. Considering that the substrate specificity of the upregulated AM MMPs includes collagenases, gelatinases, matrilysins and elastase, these data suggest that upregulated AM MMP genes and activation of MMP proteins may contribute to the emphysema of HIV1+ individuals who smoke. Keywords: expression study
2016-03-24 | GSE10038 | GEO
Project description:To begin screening global effects on osteoclast activity in an unbiased fashion, we conducted a transcriptome analysis comparing the expression profiles of wild-type, Mmp9/Mmp14 DKO osteoclasts, and Mmp9/Mmp14 DKO osteoclasts treated with GCS-100
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2014-08-27 | GSE60795 | GEO
Project description:Skin damage from solar ultraviolet radiation (UVR) accumulates in the dermal extracellular matrix (ECM) and contributes to photoaging. Following UVR exposure, matrix metalloproteinases (MMPs) are secreted by dermal fibroblasts to repair and remodel the ECM. Molecular signaling pathways delineating the induction of MMPs are currently well-defined; however, the effects of UV exposure on epigenetic mechanisms of MMP induction are not as well understood. An epigenetic mechanism would further describe how MMP genes are regulated in response to UV. In this study, we examined solar simulated UVR (ssUVR)-induced gene expression changes and alterations to histone methylation in the promoters of MMP1 and MMP3 in primary human dermal fibroblasts (HDF). This set of gene expression data was generated to identify photoaging related genes (including MMP) that were impacted by ssUVR exposure in our system.
2014-08-27 | GSE60794 | GEO
Project description:Skin damage from solar ultraviolet radiation (UVR) accumulates in the dermal extracellular matrix (ECM) and contributes to photoaging. Following UVR exposure, matrix metalloproteinases (MMPs) are secreted by dermal fibroblasts to repair and remodel the ECM. Molecular signaling pathways delineating the induction of MMPs are currently well-defined; however, the effects of UV exposure on epigenetic mechanisms of MMP induction are not as well understood. An epigenetic mechanism would further describe how MMP genes are regulated in response to UV. In this study, we examined solar simulated UVR (ssUVR)-induced gene expression changes and alterations to histone methylation in the promoters of MMP1 and MMP3 in primary human dermal fibroblasts (HDF). This set of gene expression data was generated to identify photoaging related genes (including MMP) that were impacted by ssUVR exposure in our system. Primary neonatal human dermal fibroblasts (HDF) were irradiated a single time with 12 J/cm2 ssUVR. The sham treatments are negative controls (0 J/cm2 ssUVR). The cells were collected for gene expression analysis 1 day after exposure, and then 5 days after exposure. Affymetrix GeneChip Human Exon 1.0 ST arrays were used to characterize gene expression pattern alterations in response to ssUVR.
2014-08-27 | E-GEOD-60795 | biostudies-arrayexpress