IGFBP7 aggravates sepsis-induced acute lung injury by activating the ERK1/2 pathway

Xu, Qiaolian; Wang, Jun

doi:10.5603/fhc.a2020.0028

Cited by 10 publications

(5 citation statements)

References 32 publications

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“…We then analyzed the expression of YAP1-related molecules in endothelial injury models. Consistent with previous research [ 27 ], our research also found that LPS stimulation increases the expression of IGFBP7 in endothelial cells [ 16 ]. Furthermore, LPS stimulation promotes the expression of YAP1, TEAD1, and TEAD4 molecules while reducing the expression of intracellular p-YAP1 in endothelial cells ( Figure 4 C,D).…”

Section: Resultssupporting

confidence: 93%

“…However, we also observed that supplementation of rhIGFBP7 did not promote endothelial cell proliferation in both the ALI model and the healthy control group (Supplementary Figure S2A–D). This could be due to the direct supplementation of IGFBP7 leading to damage to the endothelial barrier (Supplementary Figure S2E and S2F) [ 16 , 27 , 28 ].…”

Section: Resultsmentioning

confidence: 99%

“…However, the role of IGFBP7 in the recovery phase of inflammatory diseases is poorly understood. In ALI, pulmonary tissue injury increases IGFBP7 secretion and exacerbates sepsis-induced ALI by activating the ERK1/2 pathway [ 27 ]. Our previous studies have also shown that IGFBP7 exacerbates endothelial cell injury induced by acute-phase inflammation.…”

Section: Discussionmentioning

confidence: 99%

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IGFBP7 promotes endothelial cell repair in the recovery phase of acute lung injury

He,

Feng,

Zhang

et al. 2024

Clinical Science

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IGFBP7 has been found to play an important role in inflammatory diseases, such as acute lung injury (ALI). However, the role of IGFBP7 in different stages of inflammation remains unclear. Transcriptome sequencing was used to identify the regulatory genes of IGFBP7, and endothelial IGFBP7 expression was knocked down using Aplnr-Dre mice to evaluate the endothelial proliferation capacity. The expression of proliferation-related genes was detected by western blotting and RT-PCR assays. In this study, we found that knockdown of IGFBP7 in endothelial cells significantly decreases the expression of endothelial cell proliferation-related genes and cell number in the recovery phase but not in the acute phase of ALI. Mechanistically, using bulk-RNA sequencing and CO-IP, we found that IGFBP7 promotes phosphorylation of FOS and subsequently upregulates YAP1 molecules, thereby promoting endothelial cell proliferation. This study indicated that IGFBP7 has diverse roles in different stages of ALI, which extends the understanding of IGFBP7 in different stages of ALI and suggests that IGFBP7 as a potential therapeutic target in ALI needs to take into account the period specificity of ALI.

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Section: Resultssupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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IGFBP7 promotes endothelial cell repair in the recovery phase of acute lung injury

He,

Feng,

Zhang

et al. 2024

Clinical Science

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“…In that study, plasma IGFBP7 protein levels were the cause of increased mortality at 28 days, and the effect was mediated by platelet count [79]. Previously, upregulation of the IGFBP7 circulating levels was associated with sepsis-induced lung injury in mouse models [80] and with acute exacerbations in patients with chronic obstructive pulmonary disease [81].…”

Section: Genetic Determinants Of Ards Biomarkersmentioning

confidence: 74%

Genetic Determinants of the Acute Respiratory Distress Syndrome

Suarez-Pajes,

Tosco-Herrera,

Ramirez-Falcon

et al. 2023

JCM

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Acute respiratory distress syndrome (ARDS) is a life-threatening lung condition that arises from multiple causes, including sepsis, pneumonia, trauma, and severe coronavirus disease 2019 (COVID-19). Given the heterogeneity of causes and the lack of specific therapeutic options, it is crucial to understand the genetic and molecular mechanisms that underlie this condition. The identification of genetic risks and pharmacogenetic loci, which are involved in determining drug responses, could help enhance early patient diagnosis, assist in risk stratification of patients, and reveal novel targets for pharmacological interventions, including possibilities for drug repositioning. Here, we highlight the basis and importance of the most common genetic approaches to understanding the pathogenesis of ARDS and its critical triggers. We summarize the findings of screening common genetic variation via genome-wide association studies and analyses based on other approaches, such as polygenic risk scores, multi-trait analyses, or Mendelian randomization studies. We also provide an overview of results from rare genetic variation studies using Next-Generation Sequencing techniques and their links with inborn errors of immunity. Lastly, we discuss the genetic overlap between severe COVID-19 and ARDS by other causes.

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“…The subsequent systemic inflammation is the key to the pathogenesis of ALI. Studies have shown that the pro-inflammatory cytokines (including TNFα, IL6, and macrophage inflammatory protein 2) secreted by inflammatory cells in sepsis-induced ALI can activate neutrophils and vascular endothelial cells to initiate and maintain pulmonary inflammation [ 17 , 20 ]. GPR43 also participate in regulating the blood lipid concentration and inflammation occurrence process in human body, which is even closely related to cell carcinogenesis [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

GPR43 regulation of mitochondrial damage to alleviate inflammatory reaction in sepsis

Zhang

Wang

et al. 2021

Aging

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Sepsis is a common critical illness in ICU and always a great difficulty in clinical treatment. GPR43 (G protein-coupled receptor 43) participates in regulating appetite and gastrointestinal peptide secretion to modulate fat decomposition and formation. However, the biological contribution of GPR43 on inflammation of sepsis has not been previously investigated. We investigated the mechanisms of GPR43 gene, which plays a possible role in distinguishing sepsis and contributes to the pathogenesis of sepsis-induced inflammatory reaction. Furthermore, we performed studies with mice induced to sepsis by Cecal Ligation and Puncture (CLP), Knockout GPR43 (GPR43-/-) mice, and Wild Type (WT) mice induced with CLP. In addition, lung tissues and cell samples were analyzed by histology, Quantitative Polymerase Chain Reaction (Q-PCR), Enzyme-linked Immunosorbent (ELISA) Assay, and western blot. GPR43 agonist could significantly reduce inflammation reactions and trigger lung injury in mice with sepsis. As for GPR43-/- mice, the risks of sepsis-induced inflammatory reactions and corresponding lung injury were promoted. On the one hand, the up-regulation of GPR43 gene reduced ROS mitochondrial damage to inhibit inflammatory reactions via the inactivation of NLRP3 Inflammasome by PPARγ/ Nox1/EBP50/ p47phox signal channel. On the other hand, the down-regulation of GPR43 promoted inflammatory reactions in vitro model through the acceleration of ROS-dependently mitochondrial damage by PPARγ/ Nox1/EBP50/ p47phox/ NLRP3 signal channel. These findings indicate that the inhibition of GPR43 as a possible important factor of sepsis may shed lights on the mechanism of sepsis-induced inflammation reaction.

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IGFBP7 aggravates sepsis-induced acute lung injury by activating the ERK1/2 pathway

Cited by 10 publications

References 32 publications

IGFBP7 promotes endothelial cell repair in the recovery phase of acute lung injury

IGFBP7 promotes endothelial cell repair in the recovery phase of acute lung injury

Genetic Determinants of the Acute Respiratory Distress Syndrome

GPR43 regulation of mitochondrial damage to alleviate inflammatory reaction in sepsis

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