Structure and expression of the human gene for the matrix metalloproteinase matrilysin.

Gaire, Mireille; Magbanua, Zenaida V.; McDonnell, Susan; McNeil, Leslie Klis; Lovett, David H.; Matrisian, Lynn M.

doi:10.1016/s0021-9258(17)42131-4

Cited by 206 publications

(18 citation statements)

References 48 publications

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“…Overexpression of full-length syndecan-1 increased the amount of shed ectodomains, which aligned with previous findings [65]. Although matrix metalloproteinases with syndecan-1 sheddase activity are primarily produced by stromal cells [34,35,[66][67][68][69], MMP-7 and MMP-14 can be expressed by normal, as well as tumorous hepatocytes [56,70]. We found that MMP-7 was suppressed in cells overexpressing the truncated form of syndecan-1.…”

Section: Discussionsupporting

confidence: 91%

“…To elucidate further mechanisms by which truncated syndecan-1 suppressed syndecan-1 shedding, we examined transcriptional regulation of MMP7 and its connection to the MAPK signaling pathway, actively involved in the control of syndecan-1 shedding [71,76]. The promoter region of MMP7 contains AP-1 and PEA3 motifs, which serve as binding sites for complexes composed of members of the JUN, FOS, and ETS families of transcription factors [70,77,78]. We confirmed downregulation of the activity of promoters containing Ets-1 or AP-1 binding sites, as well as decreased Ets-1 protein expression, in cells overexpressing truncated syndecan-1.…”

Section: Discussionmentioning

confidence: 99%

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Syndecan-1 Promotes Hepatocyte-Like Differentiation of Hepatoma Cells Targeting Ets-1 and AP-1

et al. 2020

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Syndecan-1 is a transmembrane heparan sulfate proteoglycan which is indispensable in the structural and functional integrity of epithelia. Normal hepatocytes display strong cell surface expression of syndecan-1; however, upon malignant transformation, they may lose it from their cell surfaces. In this study, we demonstrate that re-expression of full-length or ectodomain-deleted syndecan-1 in hepatocellular carcinoma cells downregulates phosphorylation of ERK1/2 and p38, with the truncated form exerting an even stronger effect than the full-length protein. Furthermore, overexpression of syndecan-1 in hepatoma cells is associated with a shift of heparan sulfate structure toward a highly sulfated type specific for normal liver. As a result, cell proliferation and proteolytic shedding of syndecan-1 from the cell surface are restrained, which facilitates redifferentiation of hepatoma cells to a more hepatocyte-like phenotype. Our results highlight the importance of syndecan-1 in the formation and maintenance of differentiated epithelial characteristics in hepatocytes partly via the HGF/ERK/Ets-1 signal transduction pathway. Downregulation of Ets-1 expression alone, however, was not sufficient to replicate the phenotype of syndecan-1 overexpressing cells, indicating the need for additional molecular mechanisms. Accordingly, a reporter gene assay revealed the inhibition of Ets-1 as well as AP-1 transcription factor-induced promoter activation, presumably an effect of the heparan sulfate switch.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Syndecan-1 Promotes Hepatocyte-Like Differentiation of Hepatoma Cells Targeting Ets-1 and AP-1

et al. 2020

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“…For instance, epidermal growth factor signaling seems to increase MMP-7 levels in human colon adenocarcinoma cells. 49 Although the CX43 and PPAR-␦ genes have been identified as targets of the Wnt/␤-catenin signaling pathway in certain cell types and contexts, 20,23 neither gene has been much studied in ovarian carcinomas. In fact, in one study, connexin 43 was noted to be expressed at reduced levels in ovarian carcinomas compared to normal ovarian surface epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

Role of β-Catenin/T-Cell Factor-Regulated Genes in Ovarian Endometrioid Adenocarcinomas

Zhai

Schwartz

et al. 2002

The American Journal of Pathology

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In various cancers, inactivating mutations in the adenomatous polyposis coli or Axin tumor suppressor proteins or activating mutations in beta-catenin's amino-terminal domain elevate beta-catenin levels, resulting in marked effects on T-cell factor (TCF)-regulated transcription. Several candidate beta-catenin/TCF-regulated genes in cancer have been proposed. Expression of a few of these genes has been studied in primary human cancers, but most studies have focused on colon cancers and not on other cancer types that harbor mutational defects in adenomatous polyposis coli, AXIN, or beta-catenin. Mutations leading to beta-catenin deregulation are found in nearly half of ovarian endometrioid adenocarcinomas (OEAs). We report here on the expression of 6 candidate beta-catenin/TCF-regulated genes in a panel of 44 primary OEAs, more than a third of which carry demonstrable defects in beta-catenin regulation. Using quantitative assays of gene expression, we found significantly elevated expression of the MMP-7, CCND1 (Cyclin D1), CX43 (Connexin 43), PPAR-delta, and ITF2 genes in OEAs with deregulated beta-catenin. This correlation was not observed for c-myc, another putative beta-catenin/TCF-regulated gene. Immunohistochemical studies confirmed that overexpression of cyclin D1 and MMP-7 was highly associated with nuclear accumulation of beta-catenin and mutational defects of the Wnt/beta-catenin/TCF-signaling pathway. Our findings indicate cyclin D1, MMP-7, connexin 43, PPAR-delta, and ITF-2, likely play important roles in the pathogenesis of those OEAs that manifest defects in beta-catenin regulation.

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“…Additionally, the use of cells as drugs is still in a very preliminary stage, and the evaluation and approval of such drugs for clinical use are a long way off. On the other hand, EVs derived from MSCs have been shown to be key factors in MSC-to-surrounding cell communication [ 35 ] and are considered stem cell-based, cell-free drugs and carriers of siRNA [ 36 ]. Compared to BMSCs, BMSC-EVs have several advantages, like being simpler to produce and store and having easier quality control procedures.…”

Section: Discussionmentioning

confidence: 99%

BMSC-derived extracellular vesicles intervened the pathogenic changes of scleroderma in mice through miRNAs

Jin

Wang

et al. 2021

Stem Cell Res Ther

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Background Systemic sclerosis (SSc) is a disease that features severe fibrosis of the skin and lacks effective therapy. Bone marrow mesenchymal stem cell (BMSC)-derived extracellular vesicles (EVs) are potential stem cell-based tools for the treatment of SSc. Methods BMSCs were isolated from the bone marrow of mice and identified with surface markers according to multilineage differentiation. EVs were isolated from the BMSC culture medium by ultracentrifugation and identified with a Nanosight NS300 particle size analyzer, transmission electron microscopy (TEM), and western blot. The microRNAs (miRNAs) of BMSC-derived EVs (BMSC-EVs) were studied via miRNA sequencing (miRNA-seq) and bioinformatic analysis. An SSc mouse model was established via subcutaneous bleomycin (BLM) injection, and the mice were treated with BMSCs or BMSC-derived EVs. Skin tissues were dissociated and analyzed with H&E staining, RNA sequencing (RNA-seq), western blot, and immunohistochemical staining. Results Evident pathological changes, like fibrosis and inflammation, were induced in the skin of BLM-treated mice. BMSCs and BMSC-EVs effectively intervened such pathological manifestations and disease processes in a very similar way. The effects of the BMSC-EVs were found to be caused by the miRNAs they carried, which were proven to be involved in regulating the proliferation and differentiation of multiple cell types and in multiple EV-related biological processes. Furthermore, TGF-β1-positive cells and α-SMA-positive myofibroblasts were significantly increased in the scleroderma skin of BLM-treated mice but evidently reduced in the scleroderma skin of the EV-treated SSc group. In addition, the numbers of mast cells and infiltrating macrophages and lymphocytes were evidently increased in the skin of BLM-treated mice but significantly reduced by EV treatment. In line with these observations, there were significantly higher mRNA levels of the inflammatory cytokines Il6, Il10, and Tnf-α in SSc mice than in control mice, but the levels decreased following EV treatment. Through bioinformatics analysis, the TGFβ and WNT signaling pathways were revealed to be closely involved in the pathogenic changes seen in mouse SSc, and these pathways could be therapeutic targets for treating the disease. Conclusions BMSC-derived EVs could be developed as a potential therapy for treating skin dysfunction in SSc, especially considering that they show similar efficacy to BMSCs but have fewer developmental regulatory requirements than cell therapy. The effects of EVs are generated by the miRNAs they carry, which alleviate SSc pathogenic changes by regulating the WNT and TGFβ signaling pathways.

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Structure and expression of the human gene for the matrix metalloproteinase matrilysin.

Cited by 206 publications

References 48 publications

Syndecan-1 Promotes Hepatocyte-Like Differentiation of Hepatoma Cells Targeting Ets-1 and AP-1

Syndecan-1 Promotes Hepatocyte-Like Differentiation of Hepatoma Cells Targeting Ets-1 and AP-1

Role of β-Catenin/T-Cell Factor-Regulated Genes in Ovarian Endometrioid Adenocarcinomas

BMSC-derived extracellular vesicles intervened the pathogenic changes of scleroderma in mice through miRNAs

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