Transcriptomic Analysis of Pulmonary Microvascular Endothelial Cells with IQGAP1 Knockdown

Su, Shihong; Ai-hui, XU; Yang, Chen; Li, Wanzhen; Zha, Xiaojun; Wang, Yani; Sun, Guan

doi:10.1089/dna.2020.5451

Cited by 6 publications

(4 citation statements)

References 60 publications

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“…IQGAP1 is also reported to influence stromal cells of the lung. Recent transcriptome analysis demonstrated that IQGAP1 likely regulates cell proliferation, cell adhesion, and cell migration in pulmonary microvascular endothelial cells, as well as the production of cytokines and inflammatory factors [147]. Upon EGFR inhibitor-targeted therapy, a standard first-line treatment for NSCLC, IQGAP1 is significantly increased in microvascular endothelial cells, which decreases cell-cell adhesion, increases endothelial cell permeability, and eventually contributes to treatment-induced vascular adverse events, such as purpuric drug eruptions [148].…”

Section: Iqgap1 In Lung Cancermentioning

confidence: 99%

Role of IQGAP1 in Carcinogenesis

Tao

Lambert

2021

Cancers

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Scaffolding proteins can play important roles in cell signaling transduction. IQ motif-containing GTPase-activating protein 1 (IQGAP1) influences many cellular activities by scaffolding multiple key signaling pathways, including ones involved in carcinogenesis. Two decades of studies provide evidence that IQGAP1 plays an essential role in promoting cancer development. IQGAP1 is overexpressed in many types of cancer, and its overexpression in cancer is associated with lower survival of the cancer patient. Here, we provide a comprehensive review of the literature regarding the oncogenic roles of IQGAP1. We start by describing the major cancer-related signaling pathways scaffolded by IQGAP1 and their associated cellular activities. We then describe clinical and molecular evidence for the contribution of IQGAP1 in different types of cancers. In the end, we review recent evidence implicating IQGAP1 in tumor-related immune responses. Given the critical role of IQGAP1 in carcinoma development, anti-tumor therapies targeting IQGAP1 or its associated signaling pathways could be beneficial for patients with many types of cancer.

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Section: Iqgap1 In Lung Cancermentioning

confidence: 99%

Role of IQGAP1 in Carcinogenesis

Tao

Lambert

2021

Cancers

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“…MPMVECs were isolated from fresh lung tissues of SPF male C57BL/6 mice using a tissue block attachment method and identified according to our previous methods ( Figure S1 ). 31 , 32 Cytotoxicity of DPTP and BA@DPTP against MPMVECs were assessed using CCK-8 assay at different concentrations (0, 7.5, 15.5, 31.5, 62.5,125, 250, and 500 μg/mL) of the NPs. As shown in Figure 4A and B , the DPTP and BA@DPTP displayed no obvious cytotoxicity at concentrations ranging from 7.5 to 500 μg/mL following 12 h and 24 h of exposure.…”

Section: Resultsmentioning

confidence: 99%

Development of an Intelligent Reactive Oxygen Species-Responsive Dual-Drug Delivery Nanoplatform for Enhanced Precise Therapy of Acute Lung Injury

Xia,

Lu,

et al. 2024

IJN

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Introduction Acute lung injury (ALI) and its most severe form acute respiratory distress syndrome (ARDS) are commonly occurring devastating conditions that seriously threaten the respiratory system in critically ill patients. The current treatments improve oxygenation in patients with ALI/ARDS in the short term, but do not relieve the clinical mortality of patients with ARDS. Purpose To develop the novel drug delivery systems that can enhance the therapeutic efficacy of ALI/ARDS and impede adverse effects of drugs. Methods Based on the key pathophysiological process of ARDS that is the disruption of the pulmonary endothelial barrier, bilirubin (Br) and atorvastatin (As) were encapsulated into an intelligent reactive oxygen species (ROS)-responsive nanocarrier DSPE-TK-PEG (DPTP) to form nanoparticles (BA@DPTP) in which the thioketal bonds could be triggered by high ROS levels in the ALI tissues. Results BA@DPTP could accumulate in inflammatory pulmonary sites through passive targeting strategy and intelligently release Br and As only in the inflammatory tissue via ROS-responsive bond, thereby enhancing the drugs effectiveness and markedly reducing side effects. BA@DPTP effectively inhibited NF-κB signaling and NLRP3/caspase-1/GSDMD-dependent pyroptosis in mouse pulmonary microvascular endothelial cells. BA@DPTP not only protected mice with lipopolysaccharide-induced ALI and retained the integrity of the pulmonary structure, but also reduced ALI-related mortality. Conclusion This study combined existing drugs with nano-targeting strategies to develop a novel drug-targeting platform for the efficient treatment of ALI/ARDS.

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“…Therefore, IQGAP1 has a core role in bacterial pathogenicity as a key regulator of actin cytoskeleton dynamics. In addition, IQGAPs have been shown to choreograph cellular signaling from the membrane to the nucleus, mediating many pathophysiological processes (e.g., inflammatory regulations); IQGAP1 knockdown significantly affected many cytokines and inflammatory factors with vital roles in acute lung injury and acute respiratory distress syndrome ( 19 ). These results suggest that IQGAP1 may have multiple roles in the pathogenesis of A. baumannii infection.…”

Section: Introductionmentioning

confidence: 99%

Acinetobacter baumannii Outer Membrane Protein A Induces Pulmonary Epithelial Barrier Dysfunction and Bacterial Translocation Through The TLR2/IQGAP1 Axis

et al. 2022

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Pulmonary epithelial barrier dysfunction is a critical pathophysiological process in pneumonia and associated invasive infections, such as those caused by Acinetobacter baumannii. However, the mechanisms underlying A. baumannii-induced pulmonary epithelial barrier dysfunction and bacterial translocation remain unclear. In this study, lungs of mice and A549 human epithelial cell monolayers were challenged with the A. baumannii wild-type strain and an outer membrane protein A (ompA) deletion strain. In addition, epithelial cells in culture were treated with purified OmpA protein or transfected with a eukaryotic expression vector encoding ompA (pCMV-ompA). Bacterial translocation across cell monolayers and intrapulmonary burden were measured, barrier function was evaluated in vivo and in vitro; cell migration ability was determined. The specific inhibitors C29 and JSH-23 were used to suppress the activity of Toll-like receptor 2 (TLR2) and of NF-κB, respectively. IQ-GTPase-activating protein 1 (IQGAP1) small interfering RNA was used to knock down endogenous IQGAP1 expression. In this work, we show that OmpA from A. baumannii increased the production of pro-inflammatory cytokines, remodeled the cytoskeleton, and internalized intercellular adherens junctions (AJs); these changes eventually induced pulmonary epithelial barrier dysfunction to promote bacterial translocation. IQGAP1-targeting small interfering RNA and chemical inhibition of TLR2 or NF-κB prevented high permeability of the pulmonary epithelial barrier. TLR2/NF-κB signaling was involved in OmpA-induced inflammation, IQGAP1-mediated OmpA-induced opening of the pulmonary epithelial barrier via cytoskeleton dynamic remodeling, and cellular redistribution of the major AJ protein, E-cadherin. These observations indicate that A. baumannii uses OmpA to overcome epithelial defences and cross the pulmonary epithelial barrier.

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Transcriptomic Analysis of Pulmonary Microvascular Endothelial Cells with IQGAP1 Knockdown

Cited by 6 publications

References 60 publications

Role of IQGAP1 in Carcinogenesis

Role of IQGAP1 in Carcinogenesis

Development of an Intelligent Reactive Oxygen Species-Responsive Dual-Drug Delivery Nanoplatform for Enhanced Precise Therapy of Acute Lung Injury

Acinetobacter baumannii Outer Membrane Protein A Induces Pulmonary Epithelial Barrier Dysfunction and Bacterial Translocation Through The TLR2/IQGAP1 Axis

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