miR-10a overexpression aggravates renal ischemia–reperfusion injury associated with decreased PIK3CA expression
Abstract Background To investigate the effect of miR-10a on renal tissues with ischemia reperfusion (I/R) injury in rats and to explore the underlying mechanisms of the effect of miR-10a on hypoxia–reoxygenation in HK-2 cells. Methods MiR-10a level was measured in the renal tissues of rats with I/R...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2020-07-01
|
Series: | BMC Nephrology |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s12882-020-01898-3 |
id |
doaj-f2e4a84fe3384d65b27f5209c0c57158 |
---|---|
record_format |
Article |
spelling |
doaj-f2e4a84fe3384d65b27f5209c0c571582020-11-25T02:32:19ZengBMCBMC Nephrology1471-23692020-07-0121111110.1186/s12882-020-01898-3miR-10a overexpression aggravates renal ischemia–reperfusion injury associated with decreased PIK3CA expressionDongsheng Xu0Wenjun Li1Tao Zhang2Gang Wang3Department of Kidney Transplantation, The Second Hospital of Shandong UniversityDepartments of Thoracic Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao UniversityDepartment of Cardiac Surgery, Qingdao Fuwai Cardiovascular HospitalDepartment of Cardiac Surgery, Qingdao Fuwai Cardiovascular HospitalAbstract Background To investigate the effect of miR-10a on renal tissues with ischemia reperfusion (I/R) injury in rats and to explore the underlying mechanisms of the effect of miR-10a on hypoxia–reoxygenation in HK-2 cells. Methods MiR-10a level was measured in the renal tissues of rats with I/R rats using RT-PCR. In order to research the role of miR-10a in renal tissues, an miR-10 agonist and an miR-10a antagonist were used to treat I/R-injured rats. Levels of serum creatinine and blood urea nitrogen, renal histopathology, and levels of cell apoptosis were analyzed separately in renal tissues from the rats. Phosphatidylinositol 3-kinase (PI3K)/Akt pathway related proteins were measured by Western blotting. In addition, HK-2 cells were cultured in order to study the mechanism of action of miR-10a in the hypoxia-reoxygenation model being studied. Finally, the dual luciferase reporter gene assay was used to confirm that the PI3K p100 catalytic subunit α (PIK3CA) gene was targeted by miR-10a. Results After renal I/R injury in rats, miR-10a expression increased significantly (p < 0.05). Injection of miR-10a agonist significantly aggravated the renal injury and raised the level of cell apoptosis in the renal tissues of I/R-injured rats (p < 0.05). However, administration of miR-10a antagonist led to obvious improvement of the renal injury, decreased renal cell apoptosis, and inhibited PI3K/Akt pathway activity (p < 0.05). In in vitro experiments, the negative relationship between PIK3CA and miR-10a levels was confirmed. Furthermore, overexpression of miR-10a significantly decreased the proliferation of HK-2 cells, and increased cell apoptosis via up-regulation of the PI3K/Akt pathway (p < 0.05). Conclusion The aggravation of renal I/R injury by miR-10a was associated with a decrease in the activity of PIK3CA/PI3K/Akt pathway.http://link.springer.com/article/10.1186/s12882-020-01898-3miR-10aRenal ischemia–reperfusionHypoxia–reoxygenationPIK3CA/PI3K/Akt pathway |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dongsheng Xu Wenjun Li Tao Zhang Gang Wang |
spellingShingle |
Dongsheng Xu Wenjun Li Tao Zhang Gang Wang miR-10a overexpression aggravates renal ischemia–reperfusion injury associated with decreased PIK3CA expression BMC Nephrology miR-10a Renal ischemia–reperfusion Hypoxia–reoxygenation PIK3CA/PI3K/Akt pathway |
author_facet |
Dongsheng Xu Wenjun Li Tao Zhang Gang Wang |
author_sort |
Dongsheng Xu |
title |
miR-10a overexpression aggravates renal ischemia–reperfusion injury associated with decreased PIK3CA expression |
title_short |
miR-10a overexpression aggravates renal ischemia–reperfusion injury associated with decreased PIK3CA expression |
title_full |
miR-10a overexpression aggravates renal ischemia–reperfusion injury associated with decreased PIK3CA expression |
title_fullStr |
miR-10a overexpression aggravates renal ischemia–reperfusion injury associated with decreased PIK3CA expression |
title_full_unstemmed |
miR-10a overexpression aggravates renal ischemia–reperfusion injury associated with decreased PIK3CA expression |
title_sort |
mir-10a overexpression aggravates renal ischemia–reperfusion injury associated with decreased pik3ca expression |
publisher |
BMC |
series |
BMC Nephrology |
issn |
1471-2369 |
publishDate |
2020-07-01 |
description |
Abstract Background To investigate the effect of miR-10a on renal tissues with ischemia reperfusion (I/R) injury in rats and to explore the underlying mechanisms of the effect of miR-10a on hypoxia–reoxygenation in HK-2 cells. Methods MiR-10a level was measured in the renal tissues of rats with I/R rats using RT-PCR. In order to research the role of miR-10a in renal tissues, an miR-10 agonist and an miR-10a antagonist were used to treat I/R-injured rats. Levels of serum creatinine and blood urea nitrogen, renal histopathology, and levels of cell apoptosis were analyzed separately in renal tissues from the rats. Phosphatidylinositol 3-kinase (PI3K)/Akt pathway related proteins were measured by Western blotting. In addition, HK-2 cells were cultured in order to study the mechanism of action of miR-10a in the hypoxia-reoxygenation model being studied. Finally, the dual luciferase reporter gene assay was used to confirm that the PI3K p100 catalytic subunit α (PIK3CA) gene was targeted by miR-10a. Results After renal I/R injury in rats, miR-10a expression increased significantly (p < 0.05). Injection of miR-10a agonist significantly aggravated the renal injury and raised the level of cell apoptosis in the renal tissues of I/R-injured rats (p < 0.05). However, administration of miR-10a antagonist led to obvious improvement of the renal injury, decreased renal cell apoptosis, and inhibited PI3K/Akt pathway activity (p < 0.05). In in vitro experiments, the negative relationship between PIK3CA and miR-10a levels was confirmed. Furthermore, overexpression of miR-10a significantly decreased the proliferation of HK-2 cells, and increased cell apoptosis via up-regulation of the PI3K/Akt pathway (p < 0.05). Conclusion The aggravation of renal I/R injury by miR-10a was associated with a decrease in the activity of PIK3CA/PI3K/Akt pathway. |
topic |
miR-10a Renal ischemia–reperfusion Hypoxia–reoxygenation PIK3CA/PI3K/Akt pathway |
url |
http://link.springer.com/article/10.1186/s12882-020-01898-3 |
work_keys_str_mv |
AT dongshengxu mir10aoverexpressionaggravatesrenalischemiareperfusioninjuryassociatedwithdecreasedpik3caexpression AT wenjunli mir10aoverexpressionaggravatesrenalischemiareperfusioninjuryassociatedwithdecreasedpik3caexpression AT taozhang mir10aoverexpressionaggravatesrenalischemiareperfusioninjuryassociatedwithdecreasedpik3caexpression AT gangwang mir10aoverexpressionaggravatesrenalischemiareperfusioninjuryassociatedwithdecreasedpik3caexpression |
_version_ |
1724819913487417344 |