Dynamic changes of matrix metalloproteinases and their tissue inhibitors in severe sepsis

Mühl, Diána; Nagy, Bálint; Woth, Gábor; Falusi, Boglárka; Bogár, Lajos; Wéber, György; Lantos, János

doi:10.1016/j.jcrc.2011.02.011

Cited by 39 publications

(48 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previous experimental (Maitra et al 2010;Teng et al 2012) and clinical studies also report higher levels of TIMP-1 in sepsis (Lauhio et al 2011;Muhl et al 2011;Yazdan-Ashoori et al 2011;Lorente et al 2014) and SA-AKI .…”

Section: Discussionmentioning

confidence: 80%

“…We also found that the septic patients without SA-AKI had higher levels of MMP-9 compared to the control group which indicates that sepsis not complicated by SA-AKI, causes the increase in MMP-9 activity. In sepsis, both higher (Lauhio et al 2011;Muhl et al 2011;YazdanAshoori et al 2011;Wang et al 2014) and lower ) levels of MMP-9 were found but none of these studies reported incidence of SA-AKI in the study population.…”

Section: Discussionmentioning

confidence: 88%

“…We did not perform any power analysis due to missing pre-study data. The sample of 53 septic patients was assessed to be adequate based on previous MMP-9 and TIMP1studies in other septic patient populations (Muhl et al 2011;YazdanAshoori et al 2011;Martin et al 2014). The normality of data was assessed with Kolmogorov-Smirnov test.…”

Section: Discussionmentioning

confidence: 99%

“…We also introduced a unique control group consisting of patients without sepsis or AKI who match the septic patients by age, gender, comorbidities and a type of surgery. The previous studies on MMP-9 and TIMP-1 levels in sepsis compared septic patients to either healthy individuals (Lauhio et al 2011;Muhl et al 2011;Yazdan-Ashoori et al 2011;Wang et al 2014) or other critically ill patients or they compared different subgroups of septic patients (Lorente et al 2014) not taking into account any possible effects of surgery-induced inflammation (Helmersson-Karlqvist et al 2012;Lindholm et al 2015) or comorbidities on MMP-9 and TIMP-1 levels. Comorbidities present in patients with sepsis could alter levels of MMP-9 and TIMP-1 (Vandooren et al 2013;Galliera et al 2015) and are also considered as independent risk factors for AKI in the perioperative period (Kheterpal et al 2009).…”

Section: Discussionmentioning

confidence: 99%

“…The activity of the MMP-9 is closely regulated on multiple levels including the inhibition by regulatory proteins, such as tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) (Galliera et al 2015). Surgery-induced inflammation (Helmersson-Karlqvist et al 2012;Lindholm et al 2015) and sepsis (Muhl et al 2011;Lauhio et al 2011;Yazdan-Ashoori et al 2011;Lorente et al 2014;Wang et al 2014) are associated with altered levels of MMP-9 and TIMP-1. Increased MMP-9 and TIMP-1 expression has also been reported in a variety of AKI animal model studies (Maitra et al 2010;Teng et al 2012) but only one clinical study evaluated MMP-9 as diagnostic biomarker of AKI and not SA-AKI per se (Han et al 2008).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Diagnostic Value of Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis-Associated Acute Kidney Injury

Bojić

Kotur‐Stevuljević

Kalezić

et al. 2015

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Sepsis-associated acute kidney injury (SA-AKI) severely impacts morbidity and mortality in surgical patients with sepsis. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) have an important role in pathophysiology of sepsis but they have been unexplored in SA-AKI. We aimed to investigate the role of MMP-9 and TIMP-1 in septic surgical patients with SA-AKI and to evaluate them as diagnostic biomarkers of SA-AKI. This prospective observational study compared 53 major abdominal surgery patients with sepsis divided into SA-AKI (n = 37) and non-SA-AKI (n =16) group to 50 controls without sepsis matched by age, gender, comorbidities and type of surgery. Blood and urine samples from septic patients were collected on admission to ICU and 24, 48, 72 and 96 h later and once from the controls. The levels of MMP-9, TIMP-1, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1, urea and creatinine were measured. MMP-9/TIMP-1 ratio and disease severity scores, such as Sequential Organ Failure Assessment (SOFA), were calculated. Septic patients with SA-AKI had higher serum TIMP-1 levels and lower serum MMP-9 levels and lower MMP-9/TIMP ratio, compared to septic patients without SA-AKI and controls. The levels of these biomarkers did not change significantly over time. MMP-9, TIMP-1 and MMP-9/TIMP-1 ratio correlated with urea, creatinine, NGAL, and SOFA scores. Moreover, using the area under ROC curve, we showed that TIMP-1 and MMP-9/TIMP-1 ratio, but not MMP-9, were good diagnostic biomarkers of SA-AKI. We report for the first time the potential diagnostic value of TIMP-1 and MMP-9/TIMP-1 ratio in SA-AKI.Keywords: acute kidney injury; biomarker; matrix metalloproteinase-9; sepsis; tissue inhibitor of matrix metalloproteinase-1 Tohoku

show abstract

Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Diagnostic Value of Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis-Associated Acute Kidney Injury

Bojić

Kotur‐Stevuljević

Kalezić

et al. 2015

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

show abstract

Unraveling the immune response of the spleen in sepsis using green‐synthesized silver nanoparticles from pomegranate peel extracts

Marey,

Dkhil,

Abdel‐Moneim

et al. 2024

Microscopy Res & Technique

View full text Add to dashboard Cite

Sepsis is a serious disease characterized by an inappropriate host response to infection, resulting in widespread inflammation and systemic organ failure. The aim of this research is to investigate the possibility of pomegranate peel‐derived silver nanoparticles (PGNP) as a potential alternative therapy for sepsis. Characterization using transmission electron microscopy revealed 10–30 nm spherical nanoparticles. In a rat model of sepsis, PGNP treatment improved spleen health, histology, and immune response as compared with septic rats. In rats treated with PGNP during sepsis, significant alterations in oxidative stress markers (p < .01) were observed. These included elevated levels of glutathione (0.63 ± 0.08 mmol/mg protein), reduced concentrations of nitric oxide (8.7 ± 0.8 μ mol/mg protein) and malondialdehyde (2.2 ± 0.3 nmol/mg protein), as well as increased activity of superoxide dismutase (159 ± 33 U/mg protein). Following PGNP administration, gene expression analysis revealed a decrease in spleen IL‐1β, IL‐6, and TNF‐α, highlighting its anti‐inflammatory potential. Furthermore, PGNP effectively controlled apoptosis‐related genes (Bax, Bcl‐2, and Casp3), indicating its role in cellular survival pathways. This study sheds light on the immunological regulation of the spleen during sepsis using PGNP, demonstrating its potential as a new effective treatment approach. The study emphasizes the necessity of continuing to investigate and develop alternative medicines, particularly in light of antibiotic resistance and the global impact of sepsis.Research Highlights The study explored the potential medicinal benefits of pomegranate peel‐derived silver nanoparticles (PGNP) in the treatment of sepsis. PGNP suppressed pro‐inflammatory cytokines and enhanced the immune response. The study recommends PGNP as a viable substitute treatment.

show abstract

Increased matrix metalloproteinase‐2 in ligamentum flavum hypertrophy and the regulation of MMP‐2/TIMPs by elastin‐derived peptides

Zhuo,

Hey,

Lam

et al. 2024

Journal Orthopaedic Research

View full text Add to dashboard Cite

The study aimed to examine matrix metalloproteinase‐2 (MMP‐2) expression in a rat ligamentum flavum (LF) hypertrophy model in vivo, and the effect of elastin‐derived peptides (EDPs) on MMP‐2 and tissue inhibitors of metalloproteinases (TIMPs) in rat LF cells in vitro. Surgical destabilization was performed at the rat spinal L3/4 level to induce increased mechanical stress. Rats were killed at 6‐ and 12‐weeks postsurgery for histological staining, immunohistochemical staining, RT‐qPCR and western blot. 100 µg/mL EDPs were applied to isolated normal rat LF cells, with or without pretreatment of elastin receptor complex (ERC) inhibitors, to assess the expression of MMP‐2, TIMP‐1, and TIMP‐2. Spinal destabilization led to LF hypertrophy, observed through increased LF thickness and area, along with histological changes of chondrometaplasia and elastic fiber degradation. LF was also stained positively for Col I and Col II, where elastic fiber has broken down. MMP‐2 expression was notably elevated in the hypertrophied LF, accompanied by increased TIMP‐2 and TIMP‐3 levels. EDPs were found to suppress MMP‐2 expression and reduce TIMP‐1 and TIMP‐2 levels in rat LF cells. Interestingly, exposure to EDPs led to a significant rise in MMP‐2/TIMP‐1 and MMP‐2/TIMP‐2 ratios, dependent on the ERC. Collectively, the study suggests that increased MMP‐2 activity contributes to elastic fiber degradation in hypertrophied LF, generating EDPs that further enhance the MMP‐2/TIMPs ratio in LF cells in an ERC‐dependent manner. Further research is essential to delve into the mechanisms of EDPs in LF hypertrophy.

show abstract

Dynamic changes of matrix metalloproteinases and their tissue inhibitors in severe sepsis

Cited by 39 publications

References 27 publications

Diagnostic Value of Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis-Associated Acute Kidney Injury

Diagnostic Value of Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis-Associated Acute Kidney Injury

Unraveling the immune response of the spleen in sepsis using green‐synthesized silver nanoparticles from pomegranate peel extracts

Increased matrix metalloproteinase‐2 in ligamentum flavum hypertrophy and the regulation of MMP‐2/TIMPs by elastin‐derived peptides

Contact Info

Product

Resources

About