miR-21-3p靶向VEGFA调节PI3K/AKT信号通路对子痫前期大鼠肾损伤的影响

doi:10.3969/j.issn.1006-6233.2022.09.05

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Abstract Objective: To explore the effect of microRNA-21-3p (miR-21-3p) on renal injury in preeclampsia (PE) by targeting vascular endothelial growth factor A (VEGFA) to regulate the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway Amelioration of renal injury in rats. Methods: Sixty pregnant mice were divided into normal group, model group, mimics NC group,miR-21-3p mimics group,and miR-21-3p inhibitor group randomly. Except for the normal group, PE models were established for the remaining four groups. After successful modeling, the mimics NC group was injected with the miRNA-NC empty plasmid adenoviral vector; the miR-21-3p mimics group was injected with the adenoviral vector carrying the miR-21-3p gene; and the miR-21-3p inhibitor group was injected with the adenoviral vector carrying the miR-21-3p gene expression inhibitor, all for 7 consecutive days. At the end of the experiment, blood was collected from arteries, and the levels of SCr, BUN, IL-6, and TNF-α in serum and urinary protein in urine were measured; sections were prepared by HE staining and the renal histopathological changes were observed by light microscopy; the relative expression levels of miR-21-3p and VEGFA mRNA were detected by RT-PCR; VEGFA, PI3K, p-PI3K, AKT, p-AKT protein expression levels by Western Blot. A dual luciferase reporter gene assay was performed to verify the targeting relationship between miR-21-3p and VEGFA. Results: Compared with the normal group, the renal histopathological changes in the model group were significant, with significantly higher levels of urinary protein, SCr, BUN, TNF-α, and IL-6 (P<0.05), decreased expression of miR-21-3p in renal tissues (P<0.05), VEGFA mRNA expression as well as VEGFA, p-PI3K/PI3K and p-AKT/AKT protein expression levels were significantly increased (P<0.05). There was no significant difference in the changes of the above indicators between the mimics NC group and the model group (P>0.05). Compared with the mimics NC group, urinary protein, SCr, BUN, TNF-α, and IL-6 levels were significantly decreased in the miR-21-3p mimics group (P<0.05), miR-21-3p expression was increased in renal tissues (P<0.05), and VEGFA mRNA expression as well as VEGFA, p-PI3K/PI3K, p-AKT/ AKT protein expression levels were significantly decreased (P<0.05); SCr, BUN, urinary protein, IL-6, TNF-α levels were significantly increased in the miR-21-3p inhibitor group (P<0.05), miR-21-3p expression was decreased in renal tissues (P<0.05), VEGFA mRNA expression as well as VEGFA, p-PI3K /PI3K, p-AKT/AKT protein expression levels were significantly increased (P<0.05). Validation of the dual luciferase reporter gene assay showed that VEGFA was the target gene of miR-21-3p. Conclusion: miR-21-3p may regulate the PI3K/AKT signaling pathway by targeting VEGFA to ameliorate renal injury in PE rats.

Key words： microRNA-21-3p Vascular endothelial growth factor A Phosphatidylinositol 3-kinase/protein kinase B Preeclampsia Kidney injury

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	ZHANG Aiping
	ZHAO Dexiong
	HUO Chunxia
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ZHANG Aiping,ZHAO Dexiong,HUO Chunxia, et al. Effect of miR-21-3p Targeting VEGFA to Regulate PI3K/AKT Signaling Pathway on Renal Injury in Preeclamptic Rats[J]. HeBei Med, 2022, 28(9): 1431-1437.

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2022.09.05 OR http://www.hbyxzzs.cn/EN/Y2022/V28/I9/1431

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