Exosome-Transmitted miR-25 Induced by H. pylori Promotes Vascular Endothelial Cell Injury by Targeting KLF2

Li, Na; Liu, Shifeng; Dong, Kai; Zhang, Gui-chun; Huang, Jing; Wang, Zhiheng; Wang, Tong-jian

doi:10.3389/fcimb.2019.00366

Cited by 29 publications

(19 citation statements)

References 32 publications

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“…This communicational approach can increase the spreading scope and duration time of the signals. Recently, these nanoparticles were reported to induce some diseases, like chronic obstructive pulmonary disease and coronary heart disease 14,15 . However, the role of exosomes in ONFH is still confusing and the feasibility of exosomes in treating this disease remains unclear.…”

Section: Introductionmentioning

confidence: 99%

CD41-deficient exosomes from non-traumatic femoral head necrosis tissues impair osteogenic differentiation and migration of mesenchymal stem cells

Zhu

Guo

et al. 2020

Cell Death Dis

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Non-traumatic osteonecrosis of the femoral head (ONFH) is clinically a devastating and progressive disease without an effective treatment. Mesenchymal stem cells (MSCs) transplantation has been used to treat ONFH in early stage, but the failure rate of this therapy is high due to the reduced osteogenic differentiation and migration of the transplanted MSCs related with pathological bone tissues. However, the mechanism responsible for this decrease is still unclear. Therefore, we assume that the implanted MSCs might be influenced by signals delivered from pathological bone tissue, where the exosomes might play a critical role in this delivery. This study showed that exosomes from ONFH bone tissues (ONFH-exos) were able to induce GC-induced ONFH-like damage, in vivo and impair osteogenic differentiation and migration of MSCs, in vitro. Then, we analyzed the differentially expressed proteins (DEPs) in ONFHexos using proteomic technology and identified 842 differentially expressed proteins (DEPs). On the basis of gene ontology (GO) enrichment analysis of DEPs, fold-changes and previous report, cell adhesion-related CD41 (integrin α2b) was selected for further investigation. Our study showed that the CD41 (integrin α2b) was distinctly decreased in ONFH-exos, compared to NOR-exos, and downregulation of CD41 could impair osteogenic differentiation and migration of the MSCs, where CD41-integrin β3-FAK-Akt-Runx2 pathway was involved. Finally, our study further suggested that CD41-affluent NOR-exos could restore the glucocorticoid-induced decline of osteogenic differentiation and migration in MSCs, and prevent GC-induced ONFH-like damage in rat models. Taken together, our study results revealed that in the progress of ONFH, exosomes from the pathological bone brought about the failure of MSCs repairing the necrotic bone for lack of some critical proteins, like integrin CD41, and prompted the progression of experimentally induced ONFH-like status in the rat. CD41 could be considered as the target of early diagnosis and therapy in ONFH.

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Section: Introductionmentioning

confidence: 99%

CD41-deficient exosomes from non-traumatic femoral head necrosis tissues impair osteogenic differentiation and migration of mesenchymal stem cells

Zhu

Guo

et al. 2020

Cell Death Dis

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“…Since KLF2 is silenced by EZH2 in GC [27], increased expression of EZH2 in EBVaGC may have silenced KLF2. Li et al [59] reported that Helicobacter pylori (H. pylori) induced miR-25 to reduce the expression of KLF2. As GC can be co-infected with EBV and H. pylori, both miR-25 and miR-BART17-5p may exert a simultaneous effect on the expression of KLF2.…”

Section: Discussionmentioning

confidence: 99%

Epstein-Barr Virus miR-BART17-5p Promotes Migration and Anchorage-Independent Growth by Targeting Kruppel-Like Factor 2 in Gastric Cancer

2020

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Epstein-Barr virus (EBV) infects more than 90% of the global population and is associated with a variety of tumors including nasopharyngeal carcinoma, Hodgkin lymphoma, natural killer/T lymphoma, and gastric carcinoma. In EBV-associated gastric cancer (EBVaGC), highly expressed EBV BamHI A rightward transcripts (BART) miRNAs may contribute to tumorigenesis with limited viral antigens. Despite previous studies on the targets of BART miRNAs, the functions of all 44 BART miRNAs have not been fully clarified. Here, we used RNA sequencing data from the Cancer Genome Atlas to find genes with decreased expression in EBVaGC. Furthermore, we used AGS cells infected with EBV to determine whether expression was reduced by BART miRNA. We showed that the expression of Kruppel-like factor 2 (KLF2) is lower in AGS-EBV cells than in the AGS control. Using bioinformatics analysis, four BART miRNAs were selected to check whether they suppress KLF2 expression. We found that only miR-BART17-5p directly down-regulated KLF2 and promoted gastric carcinoma cell migration and anchorage-independent growth. Our data suggest that KLF2 functions as a tumor suppressor in EBVaGC and that miR-BART17-5p may be a valuable target for effective EBVaGC treatment.

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“…To support the role of H pylori infection in the pathogenesis of CHD via endothelial damage, Li et al showed that the presence of this microorganism increased the expression of miR‐25 in gastric epithelial cells as well as in human peripheral blood. The exosome‐associated miR‐25, through targeting of Kruppel‐like factor 2 (KLF2) in vascular endothelial cells, was involved in the regulation of the nuclear factor (NF)‐κB signaling pathway, resulting in increased expression of IL‐6, monocyte chemoattractant protein‐1 (MCP‐1), vascular cell adhesion molecule‐1 (VCAM‐1), and intercellular adhesion molecule‐1 (ICAM‐1), all markers of endothelial damage 23 …”

Section: Cardiovascular and Cerebrovascular Diseasesmentioning

confidence: 99%

Review: Extragastric diseases andHelicobacter pylori

et al. 2020

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The involvement of Helicobacter pylori infection in many extra‐gastroduodenal manifestations remains a fascinating field of investigation. However, for several of these supposed associations, the potential pathogenic mechanism remains unclear. The present review highlights the main associations of H pylori with extra‐gastroduodenal manifestations reported during the last year. We searched for the most relevant studies on this topic, published between April 2019 and March 2020, identified using the term “Helicobacter” in the MEDLINE/Pubmed database. Consistent data emerged from studies investigating metabolic syndrome and ischaemic cardiovascular diseases. Other reported fields of investigation were hepatology, especially focused on non‐alcoholic steatohepatitis, neurology, including Parkinson’s disease and Alzheimer’s disease, as well as dermatology. Inflammatory bowel disease (IBD), that comprises Crohn’s disease and ulcerative colitis, may originate from a dysregulation of the host’s immune response to commensal bacteria in individuals with genetic predisposition. The reduction of biodiversity and other specific imbalances in the faecal microbiome composition of IBD patients compared to that of healthy controls support this hypothesis. In this context, an inverse correlation between H pylori infection and IBD prevalence has been confirmed. Similar results were found in patients with kidney diseases and allergic manifestations. There are indications of the possible involvement of H pylori infection in metabolic syndrome and ischaemic cardiovascular diseases. However, due to a series of factors linked to study designs and the multifactorial pathogenesis of some diseases, further studies are needed.

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Exosome-Transmitted miR-25 Induced by H. pylori Promotes Vascular Endothelial Cell Injury by Targeting KLF2

Cited by 29 publications

References 32 publications

CD41-deficient exosomes from non-traumatic femoral head necrosis tissues impair osteogenic differentiation and migration of mesenchymal stem cells

CD41-deficient exosomes from non-traumatic femoral head necrosis tissues impair osteogenic differentiation and migration of mesenchymal stem cells

Epstein-Barr Virus miR-BART17-5p Promotes Migration and Anchorage-Independent Growth by Targeting Kruppel-Like Factor 2 in Gastric Cancer

Review: Extragastric diseases andHelicobacter pylori

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