Nuclear matrix metalloproteinase-2 in the cardiomyocyte and the ischemic-reperfused heart

Baghirova, Sabina; Hughes, Bryan; Poirier, Mathieu; Kondo, Márcia Y.; Schulz, Richard

doi:10.1016/j.yjmcc.2016.04.004

Cited by 31 publications

(26 citation statements)

References 56 publications

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“…(E) (i) E4 hearts treated with blebb ± MMP-i's (2h; n=6 hearts per lysate). pSer390 bands at intact MW (73 kDa) and 42 kDa, consistent with fragments (Baghirova, et al, 2016;Prudova, et al, 2010) predicted in silico (Song, et al, 2012). (C) Well-separated E4 CMs at 24h on gels.…”

Section: Discussionsupporting

confidence: 69%

“…We hypothesized that one or more MMPs directly degrade LMNA. Nuclear MMP2 is welldocumented for many cell types including CMs (Xie, et al, 2017), and LMNA (but not B-type lamins) has been speculated to be a proteolytic target (Baghirova, et al, 2016). Beating E4 hearts treated with MMP-i or an MMP2-specific inhibitor, MMP2-i, rescued the blebbistatin-induced decrease in LMNA in immunoblots that were also probed with a novel anti-pSer390 ( Fig.5E-…”

Section: Mechano-protection Of the Genome Is Limited By Lmna Phospho-mentioning

confidence: 79%

“…Anti-MMP2 (for both pro-and active forms) was mostly nucleoplasmic in isolated CMs with localization unaffected by actomyosin inhibition (Fig.5H). Nucleoplasmic MMP2 in neonatal CMs (Baghirova, et al, 2016;Kwan, et al, 2004) suggests that, independent of maturation stage, active MMP2 is localized appropriately for degradation of phospho-LMNA downstream of actomyosin tension ( Fig.5E-v).…”

Section: Mechano-protection Of the Genome Is Limited By Lmna Phospho-mentioning

confidence: 98%

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Mechanosensing by the lamina protects against nuclear rupture, DNA damage, and cell cycle arrest

Cho

Vashisth

Abbas

et al. 2019

Preprint

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Whether cell forces or extracellular matrix (ECM) can impact genome integrity is largely unclear.Here, acute perturbations (~1hr) to actomyosin stress or ECM elasticity cause rapid and reversible changes in lamin-A, DNA damage, and cell cycle. Embryonic hearts, differentiated iPS-cells, and various nonmuscle cell types all show that actomyosin-driven nuclear rupture causes cytoplasmic mis-localization of DNA repair factors and excess DNA damage. Binucleation and micronuclei increase as telomeres shorten, which all favor cell cycle arrest. Deficiencies in lamin-A and repair factors exacerbate these effects, but lamin-A-associated defects are rescued by repair factor overexpression and by contractility modulators in clinical trials. Contractile cells on stiff ECM normally exhibit low phosphorylation and slow degradation of lamin-A by matrix-metalloprotease-2 (MMP2), and inhibition of this lamin-A turnover and also actomyosin contractility is seen to minimize DNA damage. Lamin-A is thus stress-stabilized to mechano-protect the genome.(137 words)

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Section: Discussionsupporting

confidence: 69%

Section: Mechano-protection Of the Genome Is Limited By Lmna Phospho-mentioning

confidence: 79%

Section: Mechano-protection Of the Genome Is Limited By Lmna Phospho-mentioning

confidence: 98%

See 1 more Smart Citation

Mechanosensing by the lamina protects against nuclear rupture, DNA damage, and cell cycle arrest

Cho

Vashisth

Abbas

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…MMP-2 has been located in the nucleus of cardiomyocytes [17,28], endothelial cells [29] and neurons [25]. Closer inspection of our previous immunogold electron microscopy and immunofluorescence data [17,28] suggested to us that MMP-2 might be present within the nucleolus. Consequently, we wanted to more carefully examine the localization of nuclear MMP-2 in order to gain insight into potential MMP-2 nuclear functions.…”

Section: Mmp-2 Co-localizes With Nucleolar Markersmentioning

confidence: 81%

Matrix metalloproteinase-2 mediates ribosomal RNA transcription by cleaving nucleolar histones

Ali

García-Vilas

Cromwell

et al. 2020

Preprint

Self Cite

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Cell proliferation and survival require continuous ribosome biogenesis and protein synthesis. Genes encoding ribosomal RNA (rRNA) are physically located in a specialized substructure within the nucleus known as the nucleolus, which has a central role in the biogenesis of ribosomes. Matrix metalloproteinase-2 (MMP-2) was previously detected in the nucleus. However, its role there is elusive. Herein we report that MMP-2 resides within the nucleolus to regulate rRNA transcription. MMP-2 is enriched at the promoter region of rRNA gene repeats and its inhibition downregulates pre-rRNA transcription. The Nterminal tail of histone H3 is clipped by MMP-2 in the nucleolus and is associated with increased rRNA transcription. Knocking down/out MMP-2 or inhibiting its activity prevents histone H3 cleavage and reduces both rRNA transcription and cell proliferation. In addition to the known extracellular roles of MMP-2 in tumor growth, our data reveal an epigenetic mechanism whereby intranucleolar MMP-2 regulates cell proliferation through histone proteolysis and facilitation of rRNA transcription.

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“…Furthermore, based on the hydrolysis substrates, secreted‐type MMPs can be further classified into collagenases, gelatinases, stromelysins and matrilysins . In addition to their enzymatic activities, MMPs also exhibit a number of other pathophysiological functions independent upon their ECM hydrolysis …”

Section: Introductionmentioning

confidence: 99%

Macrophage‐derived MMP‐9 enhances the progression of atherosclerotic lesions and vascular calcification in transgenic rabbits

Chen

Waqar

Nishijima

et al. 2020

J Cellular Molecular Medi

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Matrix metalloproteinase-9 (MMP-9), or gelatinase B, has been hypothesized to be involved in the progression of atherosclerosis. In the arterial wall, accumulated macrophages secrete considerable amounts of MMP-9 but its pathophysiological functions in atherosclerosis have not been fully elucidated. To examine the hypothesis that macrophage-derived MMP-9 may affect atherosclerosis, we created MMP-9 transgenic (Tg) rabbits to overexpress the rabbit MMP-9 gene under the control of the scavenger receptor A enhancer/promoter and examined their susceptibility to cholesterol diet-induced atherosclerosis. Tg rabbits along with non-Tg rabbits were fed a cholesterol diet for 16 and 28 weeks, and their aortic and coronary atherosclerosis was compared. Gross aortic lesion areas were significantly increased in female Tg rabbits at 28 weeks; however, pathological examination revealed that all the lesions of Tg rabbits fed a cholesterol diet for either 16 or 28 weeks were characterized by increased monocyte/macrophage accumulation and prominent lipid core formation compared with those of non-Tg rabbits. Macrophages isolated from Tg rabbits exhibited higher infiltrative activity towards a chemoattractant, MCP-1 in vitro and R E FE R E N C E S 1. Gross J, Lapiere CM. Collagenolytic activity in amphibian tissues: a tissue culture assay. Additional supporting information may be found online in the Supporting Information section. How to cite this article: Chen Y, Waqar AB, Nishijima K, et al. Macrophage-derived MMP-9 enhances the progression of atherosclerotic lesions and vascular calcification in transgenic rabbits. J Cell Mol Med. 2020;24:4261-4274. https://doi.

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Nuclear matrix metalloproteinase-2 in the cardiomyocyte and the ischemic-reperfused heart

Cited by 31 publications

References 56 publications

Mechanosensing by the lamina protects against nuclear rupture, DNA damage, and cell cycle arrest

Mechanosensing by the lamina protects against nuclear rupture, DNA damage, and cell cycle arrest

Matrix metalloproteinase-2 mediates ribosomal RNA transcription by cleaving nucleolar histones

Macrophage‐derived MMP‐9 enhances the progression of atherosclerotic lesions and vascular calcification in transgenic rabbits

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