New N-arylsulfonyl-N-alkoxyaminoacetohydroxamic acids as selective inhibitors of gelatinase A (MMP-2)

Rossello, Armando; Nuti, Elisa; Orlandini, Elisabetta; Carelli, Paolo; Rapposelli, Simona; Macchia, Marco; Minutolo, Filippo; Carbonaro, Laura; Albini, Adriana; Benelli, Roberto; Cercignani, Giovanni; Murphy, Gillian; Balsamo, Aldo

doi:10.1016/j.bmc.2004.01.047

Cited by 84 publications

(63 citation statements)

References 36 publications

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“…3) (19). To confirm MMP-2 specificity, we examined MMP-2-induced TER in the presence of the specific MMP-2 inhibitor ARP100 (43,54,72) and show that ARP100 significantly blocked MMP-2-induced decreased TER (Fig. 3).…”

Section: Chymase Stimulates Intestinal Epithelial Cell Mmp-2 Productimentioning

confidence: 97%

Chymase-mediated intestinal epithelial permeability is regulated by a protease-activating receptor/matrix metalloproteinase-2-dependent mechanism

Groschwitz

Osterfeld

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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Section: Chymase Stimulates Intestinal Epithelial Cell Mmp-2 Productimentioning

confidence: 97%

Chymase-mediated intestinal epithelial permeability is regulated by a protease-activating receptor/matrix metalloproteinase-2-dependent mechanism

Groschwitz

Osterfeld

et al. 2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…The generic MMP activity in lungs was decreased to an equivalent level in X -/Y mice by the addition of this inhibitor, implying the possibility of off-target effects on other MMPs. Thus, we further analyzed the activities of MMP14 and MMP9, which have the highest possibility to be inhibited by MMPi (33). This inhibitor of MMP2 markedly suppressed the activity of MMP14 as well as MMP2, but not MMP9 (Fig.…”

Section: Mmp14-mmp2 Proteolytic Cascade Regulates Amyf Differentiationmentioning

confidence: 99%

DA-Raf–dependent inhibition of the Ras-ERK signaling pathway in type 2 alveolar epithelial cells controls alveolar formation

Watanabe-Takano

Takano

Sakamoto

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Alveolar formation is coupled to the spatiotemporally regulated differentiation of alveolar myofibroblasts (AMYFs), which contribute to the morphological changes of interalveolar walls. Although the Ras-ERK signaling pathway is one of the key regulators for alveolar formation in developing lungs, the intrinsic molecular and cellular mechanisms underlying its role remain largely unknown. By analyzing the Ras-ERK signaling pathway during postnatal development of lungs, we have identified a critical role of DA-Raf1 (DA-Raf)-a dominant-negative antagonist for the Ras-ERK signaling pathway-in alveolar formation. DA-Raf-deficient mice displayed alveolar dysgenesis as a result of the blockade of AMYF differentiation. DA-Raf is predominantly expressed in type 2 alveolar epithelial cells (AEC2s) in developing lungs, and DA-Rafdependent MEK1/2 inhibition in AEC2s suppresses expression of tissue inhibitor of matalloprotienase 4 (TIMP4), which prevents a subsequent proteolytic cascade matrix metalloproteinase (MMP)14-MMP2. Furthermore, MMP14-MMP2 proteolytic cascade regulates AMYF differentiation and alveolar formation. Therefore, DA-Raf-dependent inhibition of the Ras-ERK signaling pathway in AEC2s is required for alveolar formation via triggering MMP2 activation followed by AMYF differentiation. These findings reveal a pivotal role of the Ras-ERK signaling pathway in the dynamic regulation of alveolar development.

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“…Immunofluorescence analysis showed that either a pan-MMP inhibitor (GM6001; 5 M) (10), an MMP-2 selective inhibitor (ARP 100; 10 M) (22), or an MMP-1-sparing inhibitor (ONO-4817; 10 M) (31) all rescued the OSM-induced loss of sarcomeric ␣-actinin and titin immunostaining (Fig. 3A).…”

Section: Inhibition Of Mmp-2 Prevents Osm-induced Sarcomere Degeneratmentioning

confidence: 99%

Matrix metalloproteinase-2 in oncostatin M-induced sarcomere degeneration in cardiomyocytes

Fan

Hughes

Ali

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Cardiomyocyte dedifferentiation may be an important source of proliferating cardiomyocytes facilitating cardiac repair. Cardiomyocyte dedifferentiation and proliferation induced by oncostatin-M (OSM) is characterized by sarcomere degeneration. However, the mechanism underlying sarcomere degeneration remains unclear. We hypothesized that this process may involve matrix metalloproteinase-2 (MMP-2), a key protease localized at the sarcomere in cardiomyocytes. We tested the hypothesis that MMP-2 is involved in the sarcomere degeneration that characterizes cardiomyocyte dedifferentiation. Confocal immunofluorescence and biochemical methods were used to explore the role of MMP-2 in OSM-induced dedifferentiation of neonatal rat ventricular myocytes (NRVM). OSM caused a concentration-and time-dependent loss of sarcomeric ␣-actinin and troponin-I in NRVM. Upon OSM-treatment, the mature sarcomere transformed to a phenotype resembling a lessdeveloped sarcomere, i.e., loss of sarcomeric proteins and Z-disk transformed into disconnected Z bodies, characteristic of immature myofibrils. OSM dose dependently increased MMP-2 activity. Both the pan-MMP inhibitor GM6001 and the selective MMP-2 inhibitor ARP 100 prevented sarcomere degeneration induced by OSM treatment. OSM also induced NRVM cell cycling and increased methylthiazolyl-tetrazolium (MTT) staining, preventable by MMP inhibition. These results suggest that MMP-2 mediates sarcomere degeneration in OSM-induced cardiomyocyte dedifferentiation and thus potentially contributes to cardiomyocyte regeneration.

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New N-arylsulfonyl-N-alkoxyaminoacetohydroxamic acids as selective inhibitors of gelatinase A (MMP-2)

Cited by 84 publications

References 36 publications

Chymase-mediated intestinal epithelial permeability is regulated by a protease-activating receptor/matrix metalloproteinase-2-dependent mechanism

Chymase-mediated intestinal epithelial permeability is regulated by a protease-activating receptor/matrix metalloproteinase-2-dependent mechanism

DA-Raf–dependent inhibition of the Ras-ERK signaling pathway in type 2 alveolar epithelial cells controls alveolar formation

Matrix metalloproteinase-2 in oncostatin M-induced sarcomere degeneration in cardiomyocytes

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