دورية أكاديمية
Shiga toxin down-regulates ERG protein in endothelial cells and impairs angiogenesis.
| العنوان: | Shiga toxin down-regulates ERG protein in endothelial cells and impairs angiogenesis. |
|---|---|
| المؤلفون: | Mazzotta C; Cardiovascular Thrombosis Laboratory, Hematology/Oncology Division, Department of Pediatrics, *Massachusetts General Hospital for Children, Massachusetts General Hospital, and Harvard Medical School, United States., Ingelfinger JR; Nephology Division, Department of Pediatrics, Massachusetts General Hospital for Children, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, United States., Grabowski EF; Cardiovascular Thrombosis Laboratory, Hematology/Oncology Division, Department of Pediatrics, *Massachusetts General Hospital for Children, Massachusetts General Hospital, and Harvard Medical School, United States. Electronic address: EGRABOWSKI@mgh.harvard.edu. |
| المصدر: | Thrombosis research [Thromb Res] 2024 Aug; Vol. 240, pp. 109038. Date of Electronic Publication: 2024 May 22. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Pergamon Press Country of Publication: United States NLM ID: 0326377 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-2472 (Electronic) Linking ISSN: 00493848 NLM ISO Abbreviation: Thromb Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Elmsford, N. Y., Pergamon Press. |
| مواضيع طبية MeSH: | Down-Regulation*/drug effects , Human Umbilical Vein Endothelial Cells*/metabolism, Humans ; Transcriptional Regulator ERG/metabolism ; Shiga Toxin/metabolism ; Shiga Toxin/pharmacology ; Endothelial Cells/metabolism ; Endothelial Cells/drug effects ; von Willebrand Factor/metabolism ; Angiogenesis |
| مستخلص: | Background: Shiga toxin (Stx) can activate inflammatory signaling, leading to vascular dysfunction and promotion of a pro-thrombotic tissue microenvironment. Stx can trigger the development of the enterohemorrhagic (childhood) hemolytic uremic syndrome (eHUS), a triad of thrombocytopenia, hemolytic anemia, and acute kidney injury, often requiring dialysis. Additional features may include damage to other organs, including the gastrointestinal tract, pancreas, brain and cardiovascular system; death occurs in 2-5 %. eHUS is a thrombotic microangiopathy; thus, endothelial cell (EC) injury and platelet fibrin thrombus formation in glomerular arterioles and in the arterioles of other affected organs are likely. To elucidate mechanisms of this microangiopathy, we examined in human ECs the regulation of the platelet adhesion proteins P-selectin and von Willebrand factor (VWF), along with the downregulation of erythroblast-transformation-specific transcription factor (ERG) a key regulator of angiogenesis and megakaryocyte development. Methods: VWF, P-selectin, and ERG levels were determined using immunofluorescence and Western blot in human umbilical endothelial cells (HUVECs). HUVECs were treated with tumor necrosis factor-alpha (TNF-α), Stx-1 or both, versus normal controls. Capillary morphogenesis on Matrigel was performed using HUVECs treated, for 22 h with TNF-α, Stx-1, or both, or treated 4 h with Stx-1 alone or in combination with TNF-α for 22 h. Results: Stx-1 significantly reduced ERG and VWF expression on HUVECs, but upregulated P-selectin expression. ERG levels decreased with Stx-1 alone or in combination with TNF-α, in the nuclear, perinuclear and cytoplasmatic regions. Stx-1 reduced capillary morphogenesis, while Stx-1-TNF-α combined treatment reduced capillary morphogenesis still further. Conclusions: In the presence of Stx-1 or TNF-α or both treatments, ECs were activated, expressing higher levels of P-selectin and lower levels of VWF. Our findings, further, provide evidence that Stx-1 downregulates ERG, repressing angiogenesis in vitro. Competing Interests: Declaration of competing interest The authors declare that they have no competing interests and no conflicts of interest. (Copyright © 2024. Published by Elsevier Ltd.) |
| فهرسة مساهمة: | Keywords: Angiogenesis; Endothelial cells; P-selectin; Shiga toxin-1 Stx-1; TNF-α; VWF; erythroblast-transformation-specific transcription factor (ERG) |
| المشرفين على المادة: | 0 (Transcriptional Regulator ERG) 75757-64-1 (Shiga Toxin) 0 (ERG protein, human) 0 (von Willebrand Factor) |
| تواريخ الأحداث: | Date Created: 20240608 Date Completed: 20240705 Latest Revision: 20240705 |
| رمز التحديث: | 20240706 |
| DOI: | 10.1016/j.thromres.2024.109038 |
| PMID: | 38850807 |
| قاعدة البيانات: | MEDLINE |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 1879-2472 |
|---|---|
| DOI: | 10.1016/j.thromres.2024.109038 |