Activated α
            <sub>2</sub>
            ‐macroglobulin induces Müller glial cell migration by regulating MT1‐MMP activity through LRP1

Barcelona, Pablo F.; Jaldín-Fincati, Javier R.; Sánchez, Marı́a C.; Chiabrando, Gustavo A.

doi:10.1096/fj.12-221598

Cited by 32 publications

(45 citation statements)

References 61 publications

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“…Furthermore, it has been suggested that the intracellular traffic of MT1-MMP toward the cell surface and its participation in cellular migration may be dependent on the tumoral or nontumoral characteristics of cells, as well as on the presence of extracellular factors that induce cellular migration, such as Col-I 57 and a 2 M, 28 among others. 44 Using two-dimensional scratch wound assays, we demonstrated that, in fact, in the Three independent experiments were performed in triplicate.…”

Section: Discussionmentioning

confidence: 99%

“…In another set of experiments, to inhibit MMPs activity, cells were preincubated with GM6001 MMP inhibitor (20 nM) for 30 minutes. 28 In addition, to inhibit the activity of PI3K, cells were also pretreated with LY-294002. In all the migration experiments and to inhibit cell proliferation, cells were preincubated with 0.5 mM hydroxyurea.…”

Section: Cell Migration Assaysmentioning

confidence: 99%

“…28 Briefly, at selected times (0 and 12 hours), three random images of the wound per condition were acquired using a charge-coupled device camera (Nikon; Nikon, Inc., Melville, NY, USA) using bright-field microscopy (inverted microscope Nikon TU-2000; Nikon, Inc.) with a 103 objective (0.3 numerical aperture). Each image defined an average area of the wound equivalent to 5 3 10 5 6 1 3 10 4 lm 2 recorded to t ¼ 0 hours.…”

Section: Cell Migration Assaysmentioning

confidence: 99%

“…Whereas the MMP-9 expression was increased in MGCs stimulated by TNF-a, 22 we previously demonstrated that a 2 -macroglobulin (a 2 M), an acute-phase response protein involved in retinopathies, induces MMP-2 activation and regulates membrane type 1 MMP (MT1-MMP) activity. 28 Studies in models of CNS injury have demonstrated that the IGF-1/IGF-1R system stimulates cell migration of oligodendrocytes, 29 astrocytes, 30 and neuronal cells. 31 However, there is no information about the IGF-1 effect on MGCs' migration in retinopathies.…”

mentioning

confidence: 99%

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IGF-1 Regulates the Extracellular Level of Active MMP-2 and Promotes Müller Glial Cell Motility

Lorenc

Jaldín-Fincati

Luna

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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Citation: Lorenc VE, Jaldín-Fincati JR, Luna JD, Chiabrando GA, Sánchez MC. IGF-1 regulates the extracellular level of active MMP-2 and promotes Müller glial cell motility. Invest Ophthalmol Vis Sci. 2015;56:6948-6960. DOI:10.1167/iovs.15-17496 PURPOSE. In ischemic proliferative retinopathies, Müller glial cells (MGCs) acquire migratory abilities. However, the mechanisms that regulate this migration remain poorly understood. In addition, proliferative disorders associated with enhanced activities of matrix metalloproteinases (MMPs) also involve insulin-like growth factor (IGF)-1 participation. Therefore, the main interest of this work was to investigate the IGF-1 effect on the extracellular proteolytic activity in MGCs. METHODS.Cell culture supernatants and cell lysates of the human MGC line MIO-M1 stimulated with IGF-1 were analyzed for MMP-2 by zymographic and Western blot analysis. The MGCs' motility was evaluated by scratch wound assay. The MMP-2, b1-integrin, and focal adhesions were detected by confocal microscopy. The localization of active MMPs and actin cytoskeleton were evaluated by in situ zymography.RESULTS. The IGF-1 induced the activation of canonical signaling pathways through the IGF-1R phosphorylation. Culture supernatants showed a relative decrease in the active form of MMP-2, correlating with an increased accumulation of MMP-2 protein in the MGCs' lysate. The IGF-1 effect on MMP-2 was abolished by an IGF-1R blocking antibody, aIR3, as well as by the PI3-kinase inhibitor, LY294002. The IGF-1 increased the migratory capacity of MGCs, which was blocked by the GM6001 MMP inhibitor, LY294002 and aIR3. Finally, IGF-1 induced the intracellular distribution of MMP-2 toward cellular protrusions and the partial colocalization with b1-integrin and phospo-focal adhesion kinase signals. Gelatinase activity was concentrated along F-actin filaments.CONCLUSIONS. Taken together, these data indicate that IGF-1, through its receptor activation, regulates MGCs' motility by a mechanism that involves the MMP-2 and PI3K signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Cell Migration Assaysmentioning

confidence: 99%

Section: Cell Migration Assaysmentioning

confidence: 99%

mentioning

confidence: 99%

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IGF-1 Regulates the Extracellular Level of Active MMP-2 and Promotes Müller Glial Cell Motility

Lorenc

Jaldín-Fincati

Luna

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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“…The definitive role of these independent pathways is unclear, but it has been hypothesized that they may be responsible for internalizing different subpopulations of MT1-MMP at the cell surface, as they differ in speed and localization of internalization. A recent study revealed that α 2 M induces cellular migration of Muller glial cells by endocytic recycling and intracellular distribution of MT1-MMP toward cellular protrusions [83]. Although MT1-MMP does not bind to LRP1 directly, its activity is regulated by LRP1-mediated endocytosis via α 2 M. As discussed above, CD63 tetraspanin promotes MT1-MMP internalization and lysosomal degradation [32].…”

Section: Endocytic Regulation Of Mt-mmpsmentioning

confidence: 95%

Extracellular regulation of metalloproteinases

2015

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Matrix metalloproteinases (MMPs) and adamalysin-like metalloproteinase with thrombospondin motifs (ADAMTSs) belong to the metzincin superfamily of metalloproteinases and they play key roles in extracellular matrix catabolism, activation and inactivation of cytokines, chemokines, growth factors, and other proteinases at the cell surface and within the extracellular matrix. Their activities are tightly regulated in a number of ways, such as transcriptional regulation, proteolytic activation and interaction with tissue inhibitors of metalloproteinases (TIMPs). Here, we highlight recent studies that have illustrated novel mechanisms regulating the extracellular activity of these enzymes. These include allosteric activation of metalloproteinases by molecules that bind outside the active site, modulation of location and activity by interaction with cell surface and extracellular matrix molecules, and endocytic clearance from the extracellular milieu by low-density lipoprotein receptor-related protein 1 (LRP1).

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Standardized flow cytometry assay for identification of human monocytic heterogeneity and LRP1 expression in monocyte subpopulations: Decreased expression of this receptor in nonclassical monocytes

et al. 2014

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In this article, we present a flow cytometry assay by which human blood monocyte subpopulations-classical (CD14 11 CD16 2 ), intermediate (CD14 11 CD16 1 ), and nonclassical (CD14 1 CD16 11 ) monocytes-can be determined. Monocytic cells were selected from CD45 1 leukocyte subsets by differential staining of the low-density lipoprotein receptor-related protein 1 (LRP1), which allows reducing the spill-over of natural killer cells and granulocytes into the CD16 1 monocyte gate. Percentages of monocyte subpopulations established by this procedure were significantly comparable with those obtained by a well-standardized flow cytometry assay based on the HLA-DR monocyte-gating strategy. We also demonstrated that LRP1 is differentially expressed at cell surface of monocyte subpopulations, being significantly lower in nonclassical monocytes than in classical and intermediate monocytes. Cell surface expression of LRP1 accounts for only 20% of the total cellular content in each monocyte subpopulation. Finally, we established the within-individual biological variation (bCV%) of circulating monocyte subpopulations in healthy donors, obtaining values of 21%, 20%, and 17% for nonclassical, intermediate, and classical monocytes, respectively. Similar values of bCV% for LRP1 measured in each monocyte subpopulation were also obtained, suggesting that its variability is mainly influenced by the intrinsic biological variation of circulating monocytes. Thus, we conclude that LRP1 can be used as a third pan-monocytic marker together with CD14 and CD16 to properly identify monocyte subpopulations. The combined determination of monocyte subpopulations and LRP1 monocytic expression may be relevant for clinical studies of inflammatory processes, with special interest in atherosclerosis and cardiovascular disease. V C 2014 International Society for Advancement of Cytometry

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Activated α ₂ ‐macroglobulin induces Müller glial cell migration by regulating MT1‐MMP activity through LRP1

Cited by 32 publications

References 61 publications

IGF-1 Regulates the Extracellular Level of Active MMP-2 and Promotes Müller Glial Cell Motility

IGF-1 Regulates the Extracellular Level of Active MMP-2 and Promotes Müller Glial Cell Motility

Extracellular regulation of metalloproteinases

Standardized flow cytometry assay for identification of human monocytic heterogeneity and LRP1 expression in monocyte subpopulations: Decreased expression of this receptor in nonclassical monocytes

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Activated α 2 ‐macroglobulin induces Müller glial cell migration by regulating MT1‐MMP activity through LRP1

Cited by 32 publications

References 61 publications

IGF-1 Regulates the Extracellular Level of Active MMP-2 and Promotes Müller Glial Cell Motility

IGF-1 Regulates the Extracellular Level of Active MMP-2 and Promotes Müller Glial Cell Motility

Extracellular regulation of metalloproteinases

Standardized flow cytometry assay for identification of human monocytic heterogeneity and LRP1 expression in monocyte subpopulations: Decreased expression of this receptor in nonclassical monocytes

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Activated α ₂ ‐macroglobulin induces Müller glial cell migration by regulating MT1‐MMP activity through LRP1