Matrix metalloproteinase 9 (MMP9) limits reactive oxygen species (ROS) accumulation and DNA damage in colitis-associated cancer

Walter, Lewins; Canup, Brandon S.B.; Pujada, Adani; Bui, Tien Anh; Arbasi, Behafarin; Laroui, Hamed; Merlin, Didier; Garg, Pallavi

doi:10.1038/s41419-020-02959-z

Cited by 43 publications

(42 citation statements)

References 49 publications

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“…For example, MMP2 inhibition has been shown to sensitize lung cancer cells and MCF7 breast cancer cells to radiation, but to protect human fibroblasts from the same stress [ 42 , 43 ]. In a recent work by Walter et al [ 44 ], MMP9 expression was shown to exert a protective role in colitis-associated cancer (CAC), where MMP9 protected against ROS and reduced DNA damage, thus counteracting CAC. This suggests different MMPs may either be radio-protective or radio-sensitizing depending on the context in which they operate.…”

Section: Discussionmentioning

confidence: 99%

MT1-MMP-dependent ECM processing regulates laminB1 stability and mediates replication fork restart

Thakur

Freitas

et al. 2021

PLoS ONE

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Radiotherapy remains a mainstay of treatment for a majority of cancer patients. We have previously shown that the membrane bound matrix metalloproteinase MT1-MMP confers radio- and chemotherapy resistance to breast cancer via processing of the ECM and activation of integrinβ1/FAK signaling. Here, we further discovered that the nuclear envelope protein laminB1 is a potential target of integrinβ1/FAK. FAK interacts with laminB1 contributing to its stability. Stable laminB1 is found at replication forks (RFs) where it is likely to allow the proper positioning of RF protection factors, thus preventing RF degradation. Indeed, restoration of laminB1 expression rescues replication fork stalling and collapse that occurs upon MT1-MMP inhibition, and reduces DNA damage in breast cancer cells. Together, these data highlight a novel mechanism of laminB1 stability and replication fork restart via MT1-MMP dependent extracelluar matrix remodeling.

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Section: Discussionmentioning

confidence: 99%

MT1-MMP-dependent ECM processing regulates laminB1 stability and mediates replication fork restart

Thakur

Freitas

et al. 2021

PLoS ONE

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“…The inflammageing concept also includes oxidative stress, and herein we see a sex-specific association between MMP-9 and 8-OHdG, a nuclear and mitochondrial DNA stress marker, in ESKD males only. The negative relationship might be explained by the compensatory activation of endogenous antioxidants that suppress 8-OHdG [49]. Previously reported within this cohort, which was a sub-group for the current biomarker analysis, 8-OHdG showed a sex-adjusted association with all-cause mortality in CKD patients independent of inflammation markers [50].…”

Section: Discussionmentioning

confidence: 59%

Role of GDF-15, YKL-40 and MMP 9 in patients with end-stage kidney disease: focus on sex-specific associations with vascular outcomes and all-cause mortality

et al. 2021

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Background Sex differences are underappreciated in the current understanding of cardiovascular disease (CVD) in association with chronic kidney disease (CKD). A hallmark of CKD is vascular aging that is characterised, amongst others, by; systemic inflammation, microbiota disbalance, oxidative stress, and vascular calcification—features linked to atherosclerosis/arteriosclerosis development. Thus, it is the necessary to introduce novel biomarkers related to athero-/arteriosclerotic damage for better assessment of vascular ageing in patients CKD. However, little is known about the relationship between uraemia and novel CVD biomarkers, such as growth differentiation factor-15 (GDF-15), cartilage glycoprotein-39 (YKL-40) and matrix metalloproteinase-9 (MMP-9). Therefore, we hypothesise that there are sex-specific relationships between GDF-15, YKL-40, MMP-9 levels in end-stage kidney disease (ESKD) patients in relation to gut microbiota, vascular calcification, inflammation, comorbidities, and all-cause mortality. Methods ESKD patients, males (n = 151) and females (n = 79), not receiving renal replacement therapy were selected from two ongoing prospective ESKD cohorts. GDF-15, YKL-40 and MMP9 were analysed using enzyme-linked immunosorbent assay kits. Biomarker levels were analysed in the context of gut microbiota-derived trimethylamine N-oxide (TMAO), vascular calcification, inflammatory response, oxidative stress, comorbidities, and all-cause mortality. Results Increased GDF-15 correlated with higher TMAO in females only, and with higher coronary artery calcification and IL-6. In females, diabetes was associated with elevated GDF-15 and MMP-9, whilst males with diabetes only had elevated GDF-15. No associations were found between biomarkers and CVD comorbidity. Deceased males and females had higher GDF-15 concentrations (p = 0.01 and p < 0.001, respectively), meanwhile only YKL-40 was increased in deceased males (p = 0.02). Conclusions In conclusion, in males GDF-15 and YKL-40 were related to vascular calcification, inflammation, and oxidative stress, whilst in females GDF-15 was related to TMAO. Increased levels of YKL-40 and GDF-15 in males, and only GDF-15 in females, were associated with all-cause mortality. Our findings suggest that sex-specific associations of novel CVD biomarkers have a potential to affect development of cardiovascular complications in patients with ESKD.

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“…IL-1β and IL-8 are essential inflammatory cytokines; MMP-9 facilitates the transformation of the inactive precursor IL-1β into active IL-1β by activating the IL-1β invertase (10) and pyrolyzes IL-8 to enhance its chemotactic activity and further aggravate the inflammatory response (11). In inflammatory diseases, MMP-9 gene silencing can also restrict ROS accumulation (29), obstruct MMP-9 activation, repress the redox reaction, and relieve neuroinflammation (30). The present study showed that high MMP-9 expression further enhanced the oxidative stress and inflammatory responses to ox-LDL.…”

Section: Discussionmentioning

confidence: 99%

Ox-LDL Aggravates the Oxidative Stress and Inflammatory Responses of THP-1 Macrophages by Reducing the Inhibition Effect of miR-491-5p on MMP-9

Liao

Zhu

Wan-xing

2021

Front. Cardiovasc. Med.

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Background: Oxidized low-density lipoprotein (ox-LDL) can induce oxidative stress and inflammatory responses in macrophages to facilitate the genesis and development of atherosclerosis. However, the intermediate links remain unclear. MiR-491-5P can inhibit matrix metalloproteinase 9 (MMP-9); however, it remains unclear whether ox-LDL enhances MMP-9 expression and aggravates the oxidative stress and inflammatory responses under the mediating effect of miR-491-5P.Method: THP-1 macrophages were divided into 10 groups: blank (control), model (ox-LDL), miR-491-5P high-expression (miR-491-5P mimic), miR-491-5P control (mimic-NC), MMP-9 high-expression (MMP-9-plasmid), MMP-9 control (plasmid-NC), miR-491-5P+plasmid-NC, miR-491-5P+ MMP-9-plasmid, MMP-9 gene silencing (MMP-9-siRNA), and gene silencing control (siRNA-NC). The cells were transfected for 48 h and then treated with 50 μg/mL of ox-LDL for 24 h. MMP-9 mRNA and miR-491-5P expression levels in the cells were detected using reverse transcription-quantitative polymerase chain reaction, and the MMP-9 levels were detected with western blotting. The levels of oxidative stress factors (malondialdehyde [MDA]), reactive oxygen species (ROS), and antioxidant factors (superoxide dismutase [SOD]), and the expression levels of inflammatory factors (tumor necrosis factor [TNF-α] and interleukin-1β and−6 [IL-1β and IL-6]) in the supernatant were detected with enzyme-linked immunosorbent assay.Results: MDA, ROS, TNF-α, IL-1β, IL-6, and MMP-9 levels were increased, SOD activity was reduced, and miR-491-5P expression was downregulated in the ox-LDL group compared to the control group. In the miR-491-5P mimic group, the MDA, ROS, TNF-α, IL-1β, IL-6, MMP-9 mRNA and protein levels were downregulated, and SOD activity was enhanced compared to the ox-LDL group. MMP-9-plasmid elevated the MDA, ROS, TNF-α, IL-1β, IL-6, MMP-9 mRNA and protein levels, and downregulated SOD activity and miR-491-5P expression. Following transfection with MMP-9-siRNA, the MMP-9-plasmid outcomes were nullified, and the resulting trends were similar to the miR-491-5p simulation group. Oxidative stress and inflammatory responses were higher in the miR-491-5P mimic+MMP-9-plasmid co-transfection group than in the miR-491-5P mimic group.Conclusion: Ox-LDL aggravates the oxidative stress and inflammatory responses of THP-1 macrophages by reducing the inhibition effect of miR-491-5p on MMP-9.

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Matrix metalloproteinase 9 (MMP9) limits reactive oxygen species (ROS) accumulation and DNA damage in colitis-associated cancer

Cited by 43 publications

References 49 publications

MT1-MMP-dependent ECM processing regulates laminB1 stability and mediates replication fork restart

MT1-MMP-dependent ECM processing regulates laminB1 stability and mediates replication fork restart

Role of GDF-15, YKL-40 and MMP 9 in patients with end-stage kidney disease: focus on sex-specific associations with vascular outcomes and all-cause mortality

Ox-LDL Aggravates the Oxidative Stress and Inflammatory Responses of THP-1 Macrophages by Reducing the Inhibition Effect of miR-491-5p on MMP-9

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