RETRACTED: Ghrelin Alleviates Intestinal Dysfunction in Sepsis Through the KLF4/MMP2 Regulatory Axis by Activating SIRT1

Li, Bin; Dou, Zhimin; Zhang, Lei; Zhu, Lei; Cao, Yongqiang; Yu, Qin

doi:10.3389/fimmu.2021.646775

Cited by 13 publications

(16 citation statements)

References 37 publications

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“…The Effect of 3PO on the Intestinal Pathological Changes and Permeability. Light microscopy showed that the villi in the small intestinal mucosa of the sepsis mice were thinner, shorter, and more disorderly arranged, with cell shedding at the top of the villi, consistent with previous studies [17,18]. The microvilli became thinner and shorter, and some microvilli were destroyed (Figure 3(a)).…”

Section: Oxidative Medicine and Cellular Longevitysupporting

confidence: 90%

Inhibition of PFKFB Preserves Intestinal Barrier Function in Sepsis by Inhibiting NLRP3/GSDMD

Zhang

Liu

Xie

et al. 2022

Oxidative Medicine and Cellular Longevity

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Intestinal barrier dysfunction is associated with the occurrence and development of sepsis. Further, aerobic glycolysis plays an essential role in inflammation and cell death. This study is aimed at investigating the protective effect and mechanism of PFKFB3 inhibition on intestinal barrier dysfunction in sepsis mice. Sepsis mouse models were established by cecal ligation and puncture (CLP) in wild-type mice and Gsdmd-/- mice. The results showed that the expression of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) in the small intestines was significantly upregulated in sepsis. 3-(3-Pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), the specific inhibitor of PFKFB3, and Gsdmd gene knockout significantly inhibited the inflammatory response and cell death caused by sepsis, thus alleviating intestinal damage and barrier dysfunction. 3PO was also shown to significantly inhibit oxidative stress and NLRP3/caspase-1/GSDMD-dependent cell pyroptosis in the small intestines. The in vitro studies revealed that 3PO reduced NLRP3/caspase-1/GSDMD-dependent cell pyroptosis by inhibiting ROS. Taken together, our results suggest that PFKFB3 is involved in inflammation, oxidative stress, and pyroptosis during sepsis and enhances intestinal damage, which may provide important clues about the potential targets to be exploited in this highly lethal disease.

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Section: Oxidative Medicine and Cellular Longevitysupporting

confidence: 90%

Inhibition of PFKFB Preserves Intestinal Barrier Function in Sepsis by Inhibiting NLRP3/GSDMD

Zhang

Liu

Xie

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Its substrate can be used to connect ferritin protein shell and molecule drugs and then connect to the surface of the nanocage, thus stimulating the nanomedicine system ( Lee et al, 2015 ; Xu et al, 2019 ). Otherwise, MMP2 was demonstrated to be a key regulator in sepsis ( Li B. et al, 2021 ). Xu et al (2019) revealed a combined chemotherapy and photodynamic therapy by transporting the MMP2-triggered nanodrugs into the tumor sites.…”

Section: Discussionmentioning

confidence: 99%

Synergistic effect of GF9 and streptomycin on relieving gram-negative bacteria-induced sepsis

Wei

2022

Front. Bioeng. Biotechnol.

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Triggering receptor expressed on myeloid cells-1 (TREM-1) regulates inflammation and promotes a vigorous immune response. GF9 is one of the peptides that inhibit the mTREM-1 signaling pathway, thus reducing the inflammatory mediators in diseases including sepsis. Nanotechnology could offer a new complementary strategy for diseases. Streptomycin is also one treatment of sepsis. However, the role of nanoparticles delivered GF9 combined with streptomycin on sepsis had never been discovered. In the present study, cecal ligation and puncture (CLP) and lipopolysaccharide [LPS, Escherichia coli (E. coli) O111:B4] sepsis models were constructed. SDS-PAGE was used to evaluate the size of nano drugs; Western blot was used to detect the protein levels of MMP2 and TREM-1 in cells. The levels of TNF-α and IL-6 were detected by ELISA. Histopathological changes were observed by HE staining. And the nanomedicines of GF9-HFn/Str were successfully constructed. The size of GF9-HFn/Str is 36 kD. The ferritin-based nanoparticle plays a vital role in delivering streptomycin into cells and tissues. GF9 (1.6 μM) and streptomycin (40 μM) co-delivery nanomedicine showed a better effect on promoting overall survival, decreasing E. coli, significantly suppressed the expression levels of inflammatory factors (TNF-α and IL-6), and can reduce lung injury. Our study demonstrated that combination delivery of nanomedicine GF9 and streptomycin have a better effect on overall survival rate, anti-inflammatory, and anti-bacterial in sepsis. Our present study revealed a new potential therapeutic method for sepsis.

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“…Anna Vasku et al, reported that rs243864 SNP is located at promotor site of the MMP2 gene and three transcriptional factors can be bind with only T allele of rs243864 but not with G allele [ 50 ]. One of those transcriptional factors, which is the gut-enriched Krüppel-like factor (KLF4) and Bin Li et al, found KLF4 downregulates MMP2 expression [ 51 ]. This means in the presence of rs243864 T allele, KLF4 inhibits MMP2 expression.…”

Section: Discussionmentioning

confidence: 99%

SNP-SNP positive interaction between MMP2 and MMP12 increases the risk of COPD

Ganbold,

Jamiyansuren,

Munkhzorig

et al. 2024

PLoS ONE

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Determining SNP-SNP interaction of the disease has become important for further investigation of pathogenesis and experimental research. Although many studies have been published on the effect of MMPs gene polymorphisms on chronic obstructive pulmonary disease (COPD), there is a lack of information on SNP-SNP and SNP-environment interactions. This study aimed to investigate the interaction between the polymorphisms of MMP1, MMP2, MMP9 and MMP12 genes and its combined effect with smoking on the risk of developing COPD. Totally 181 COPD patients and 292 healthy individuals were involved. Blood samples from the participants were tested for genotyping and data were collected through questionnaires. Genotyping was performed with nested allele-specific polymerase chain reaction (AS-PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). SNP-SNP and SNP-environment interactions were investigated using multifactor dimensionality reduction and logistic regression analysis. The result showed that participants with high nicotine dependence and heavy smokers had a higher risk of COPD than non-smokers. Also, G/G genotype (cOR = 5.83; 95% CI, 1.19–28.4, p = 0.029) of MMP2 rs243864 and T/T genotype (cOR = 1.79; 95% CI, 1.16–2.76, p = 0.008) of MMP12 rs652438 independently contributes to the susceptibility of COPD. For SNP-SNP interaction, the positive interaction between rs243864 G/G genotype of MMP2 and rs652438 T/T genotype of MMP12 was found, and the combination of risk genotypes has a high risk of COPD (OR = 12.92; 95% CI, 1.46–114.4, p = 0.021). Moreover, the combination of T/T genotype of MMP12 rs652438 and smoking-related factors increases the risk of COPD approximately 4.5 to 6-fold. The results suggests that there is a combination of MMP2, MMP12, and smoking-related factors may increase the risk of developing COPD.

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RETRACTED: Ghrelin Alleviates Intestinal Dysfunction in Sepsis Through the KLF4/MMP2 Regulatory Axis by Activating SIRT1

Cited by 13 publications

References 37 publications

Inhibition of PFKFB Preserves Intestinal Barrier Function in Sepsis by Inhibiting NLRP3/GSDMD

Inhibition of PFKFB Preserves Intestinal Barrier Function in Sepsis by Inhibiting NLRP3/GSDMD

Synergistic effect of GF9 and streptomycin on relieving gram-negative bacteria-induced sepsis

SNP-SNP positive interaction between MMP2 and MMP12 increases the risk of COPD

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