Nrp-1 Mediated Plasmatic Ago2 Binding miR-21a-3p Internalization: A Novel Mechanism for miR-21a-3p Accumulation in Renal Tubular Epithelial Cells during Sepsis
Joint Authors
Liu, Zhongwei
Zheng, Shixiang
Zou, Zhiqiang
Lin, Qin
Yang, Huobao
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-08-19
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
The mechanism underlying sepsis-associated acute kidney injury (SAKI), which is an independent risk factor for sepsis-associated death, is unclear.
A previous study indicates that during sepsis miR-21a-3p accumulates in renal tubular epithelial cells (TECs) as the mediator of inflammation and mediates TEC malfunction by manipulating its metabolism.
However, the specific mechanism responsible for the accumulation of miR-21a-3p in TECs during sepsis is unrevealed.
In this study, a cecal ligation and puncture- (CLP-) induced sepsis rat model and rat TEC line were used to elucidate the mechanism.
Firstly, miR-21a-3p and Ago2 levels were found out to increase in both plasma and TECs during sepsis, and the increase of intracellular Ago2 and miR-21a-3p could be mitigated when Ago2 was either inactivated or downregulated in septic plasma.
Moreover, membrane Nrp-1 expression of TECs was increased significantly during sepsis and Nrp-1 knockdown also mitigated the rise of both the intracellular Ago2 and miR-21a-3p levels in TECs incubated with septic plasma.
Furthermore, it was revealed that Ago2 can be internalized by TECs mediated with Nrp-1 and this process had no effect on the intracellular content of miR-21a-3p.
Both Ago2 and miR-21a-3p could bind to TECs derived Nrp-1 directly.
Finally, it was determined that miR-21a-3p was internalized by TECs via Nrp-1 and Ago2 facilitated this process.
Taken together, it can be concluded from our results that Ago2 binding miR-21a-3p from septic plasma can be actively internalized by TECs via Nrp-1 mediated cell internalization, and this mechanism is crucial for the rise of intracellular miR-21a-3p content of TECs during sepsis.
These findings will improve our understanding of the mechanisms underlying SAKI and aid in developing novel therapeutic strategies.
American Psychological Association (APA)
Zou, Zhiqiang& Lin, Qin& Yang, Huobao& Liu, Zhongwei& Zheng, Shixiang. 2020. Nrp-1 Mediated Plasmatic Ago2 Binding miR-21a-3p Internalization: A Novel Mechanism for miR-21a-3p Accumulation in Renal Tubular Epithelial Cells during Sepsis. BioMed Research International،Vol. 2020, no. 2020, pp.1-15.
https://search.emarefa.net/detail/BIM-1132458
Modern Language Association (MLA)
Zou, Zhiqiang…[et al.]. Nrp-1 Mediated Plasmatic Ago2 Binding miR-21a-3p Internalization: A Novel Mechanism for miR-21a-3p Accumulation in Renal Tubular Epithelial Cells during Sepsis. BioMed Research International No. 2020 (2020), pp.1-15.
https://search.emarefa.net/detail/BIM-1132458
American Medical Association (AMA)
Zou, Zhiqiang& Lin, Qin& Yang, Huobao& Liu, Zhongwei& Zheng, Shixiang. Nrp-1 Mediated Plasmatic Ago2 Binding miR-21a-3p Internalization: A Novel Mechanism for miR-21a-3p Accumulation in Renal Tubular Epithelial Cells during Sepsis. BioMed Research International. 2020. Vol. 2020, no. 2020, pp.1-15.
https://search.emarefa.net/detail/BIM-1132458
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1132458