scholarly journals Endothelial progenitor cells-derived exosomal microRNA-21-5p alleviates sepsis-induced acute kidney injury by inhibiting RUNX1 expression

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Yue Zhang ◽  
Hongdong Huang ◽  
Wenhu Liu ◽  
Sha Liu ◽  
Xue Yan Wang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Endothelial Glycocalyx ◽  
Endothelial Progenitor ◽  
Marker Proteins ◽  
Related Transcription Factor

AbstractThe role of microRNA-21-5p (miR-21-5p) in sepsis-induced acute kidney injury (AKI) has been seldom discussed. Therefore, the objective of this present study was to investigate the mechanism of endothelial progenitor cells-derived exosomes (EPCs-exos) in sepsis-induced AKI via miR-21-5p/runt-related transcription factor 1 (RUNX1) axis. miR-21-5p was downregulated and RUNX1 was upregulated in the kidney of cecal ligation and puncture (CLP) rats, and miR-21-5p targeted RUNX1. Elevation of miR-21-5p improved renal function and renal tissue pathological damage, attenuated serum inflammatory response, as well as reduced apoptosis and oxidative stress response in renal tissues, and regulated endothelial glycocalyx damage marker proteins syndecan-1 and heparanase-1 in CLP rats. Overexpression of RUNX1 abolished the impacts of elevated miR-21-5p in CLP rats. Also, EPCs-exos upregulated miR-21-5p expression, and functioned similar to elevation of miR-21-5p for CLP rats. Downregulating miR-21-5p partially reversed the effects of EPCs-exos on sepsis-induced AKI. Collectively, our study suggests that EPCs release miR-21-5p-containing exosomes to alleviate sepsis-induced AKI through RUNX1 silencing.

scholarly journals FGF23 ameliorates ischemia-reperfusion induced acute kidney injury via modulation of endothelial progenitor cells: targeting SDF-1/CXCR4 signaling

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Huang-Ming Chang ◽  
Kang-Yung Peng ◽  
Chieh-Kai Chan ◽  
Chiao-Yin Sun ◽  
Ying-Ying Chen ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Ischemia Reperfusion ◽  
Fibroblast Growth Factor 23 ◽  
Kidney Injury ◽  
In Vitro Assays ◽  
Tubular Damage ◽  
Endothelial Progenitor ◽  
Cxcr4 Signaling

AbstractThe levels of fibroblast growth factor 23 (FGF23) rapidly increases after acute kidney injury (AKI). However, the role of FGF23 in AKI is still unclear. Here, we observe that pretreatment with FGF23 protein into ischemia-reperfusion induced AKI mice ameliorates kidney injury by promoting renal tubular regeneration, proliferation, vascular repair, and attenuating tubular damage. In vitro assays demonstrate that SDF-1 induces upregulation of its receptor CXCR4 in endothelial progenitor cells (EPCs) via a non-canonical NF-κB signaling pathway. FGF23 crosstalks with the SDF-1/CXCR4 signaling and abrogates SDF-1-induced EPC senescence and migration, but not angiogenesis, in a Klotho-independent manner. The downregulated pro-angiogenic IL-6, IL-8, and VEGF-A expressions after SDF-1 infusion are rescued after adding FGF23. Diminished therapeutic ability of SDF-1-treated EPCs is counteracted by FGF23 in a SCID mouse in vivo AKI model. Together, these data highlight a revolutionary and important role that FGF23 plays in the nephroprotection of IR-AKI.

The Role of Endothelial Progenitor Cells in Acute Kidney Injury

2009 ◽  
Vol 27 (3) ◽  
pp. 261-270 ◽  
Author(s):  
Francesca Becherucci ◽  
Benedetta Mazzinghi ◽  
Elisa Ronconi ◽  
Anna Peired ◽  
Elena Lazzeri ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Kidney Injury ◽  
Endothelial Progenitor

scholarly journals In acute kidney injury, indoxyl sulfate impairs human endothelial progenitor cells: modulation by statin

Angiogenesis ◽  
2013 ◽  
Vol 16 (3) ◽  
pp. 609-624 ◽  
Author(s):  
Vin-Cent Wu ◽  
◽  
Guang-Huar Young ◽  
Po-Hsun Huang ◽  
Shyh-Chyi Lo ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Kidney Injury ◽  
Indoxyl Sulfate ◽  
Endothelial Progenitor

scholarly journals Constitutive Atg5 overexpression in mouse bone marrow endothelial progenitor cells improves experimental acute kidney injury

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Daniel Patschan ◽  
Katrin Schwarze ◽  
Björn Tampe ◽  
Jan Ulrich Becker ◽  
Samy Hakroush ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Kidney Injury ◽  
Mouse Bone Marrow ◽  
Protective Effects ◽  
Endothelial Progenitor ◽  
Matrix Deposition ◽  
Peritubular Capillaries ◽  
Clinical Consequences

Abstract Background Endothelial Progenitor Cells have been shown as effective tool in experimental AKI. Several pharmacological strategies for improving EPC-mediated AKI protection were identified in recent years. Aim of the current study was to analyze consequences of constitutive Atg5 activation in murine EPCs, utilized for AKI therapy. Methods Ischemic AKI was induced in male C57/Bl6N mice. Cultured murine EPCs were systemically injected post-ischemia, either natively or after Atg5 transfection (Adenovirus-based approach). Mice were analyzed 48 h and 6 weeks later. Results Both, native and transfected EPCs (EPCsAtg5) improved persisting kidney dysfunction at week 6, such effects were more pronounced after injecting EPCsAtg5. While matrix deposition and mesenchymal transdifferentiation of endothelial cells remained unaffected by cell therapy, EPCs, particularly EPCsAtg5 completely prevented the post-ischemic loss of peritubular capillaries. The cells finally augmented the augophagocytic flux in endothelial cells. Conclusions Constitutive Atg5 activation augments AKI-protective effects of murine EPCs. The exact clinical consequences need to be determined.

scholarly journals Constitutive Atg5 overexpression in mouse bone marrow endothelial progenitor cells improves experimental acute kidney injury

2019 ◽  
Author(s):  
daniel patschan ◽  
Katrin Schwarze ◽  
Oliver Ritter ◽  
Susann Patschan ◽  
Gerhard Anton Müller
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Kidney Injury ◽  
Mouse Bone Marrow ◽  
Protective Effects ◽  
Kidney Dysfunction ◽  
Endothelial Progenitor ◽  
Matrix Deposition ◽  
Peritubular Capillaries ◽  
Clinical Consequences

Abstract Background Endothelial Progenitor Cells have been shown as effective tool in experimental AKI. Several pharmacological strategies for improving EPC-mediated AKI protection were identified in recent years. Aim of the current study was to analyze consequences of constitutive Atg5 activation in murine EPCs, utilized for AKI therapy.Methods Ischemic AKI was induced in male C57/Bl6N mice. Cultured murine EPCs were systemically injected post-ischemia, either natively or after Atg5 transfection (Adenovirus-based approach). Mice were analyzed 48 hours and 6 weeks later.Results Both, native and transfected EPCs (EPCsAtg5) improved persisting kidney dysfunction at week 6, such effects were more pronounced after injecting EPCsAtg5. While matrix deposition and mesenchymal transdifferentiation of endothelial cells remained unaffected by cell therapy, EPCs, particularly EPCsAtg5 completely prevented the post-ischemic loss of peritubular capillaries. The cells finally augmented the augophagocytic flux in endothelial cells.Conclusions Constitutive Atg5 activation augments AKI-protective effects of murine EPCs. The exact clinical consequences need to be determined.

scholarly journals MO334ERYTHROPOIETIN-STIMULATED HUMAN ENDOTHELIAL PROGENITOR CELLS AMELIORATE INFLAMMATION AND FIBROSIS VIA INFLAMMASOME IN ISCHEMIA/REPERFUSION-INDUCED ACUTE KIDNEY INJURY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Ha Nee Jang ◽  
Jin Hyun Kim ◽  
Seunghye Lee ◽  
Sehyun Jung ◽  
Se-Ho Chang ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Tissue Injury ◽  
Apoptotic Cell ◽  
Human Peripheral Blood ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Endothelial Damage ◽  
Endothelial Progenitor ◽  
Erythroid Progenitor

Abstract Background and Aims Ischemia/reperfusion-induced AKI (IR-AKI) is a major cause of AKI and progress to chronic kidney disease. But an effective therapeutic intervention for IR-AKI is not established yet. Erythropoietin (EPO) is a potent stimulator of erythroid progenitor cells and is significantly upregulated during hypoxia. Endothelial progenitor cells (EPCs) are derived from the bone marrow or tissue-resident cells and play major roles in the maintenance of vascular integrity and the repair of endothelial damage. So, we investigated if EPO-stimulated human EPCs could have the renoprotective effects in an IR-AKI mouse model. Method EPCs originated from human peripheral blood were cultured with EPO (10 IU/mL). Mice were assigned to sham, IR only groups, IR with EPC, and IR with EPO-treated EPC. EPCs (5x105 cells, tail vein) were administered twice at 30 min prior to bilateral renal artery occlusion, and 5 min before reperfusion, with all mice sacrificed 24 h after IR-AKI. Results Both EPCs and EPO-treated EPCs significantly attenuated the renal dysfunction associated with IR-AKI, as well as tissue injury. Apoptotic cell death and oxidative stress were significantly reduced in EPC and EPO-treated EPC mice. Expression of PCNA, ICAM-1, MCP-1 and α-SMA were also significantly reduced in EPC and EPO-treated EPC mice. Furthermore, the expression of NLRP3 and caspase-1 via the activation of NF-κB signaling pathways were significantly reduced in EPC and EPO-treated EPC mice. These results show more effective in EPO-treated EPC than EPC alone and suggest EPO might be involved in the development of EPC. Conclusion This study provides that inflammasome-mediated inflammation and fibrosis might be a potential target of EPC as a treatment for IR-AKI.

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