TFAP2C Attenuates Hypertensive Endothelial Dysfunction by Transcriptionally Activating SPRY4: A Novel Axis Regulated by miR-3656.

Authors

Yaxuan Ren, Xinxin Fan, Yu Tian, Junbo Zhan, Xinmeng Hu, Yawen Liu, Yi Cheng

Published in

FASEB journal : official publication of the Federation of American Societies for Experimental Biology. Volume 40. Issue 22. Nov 30, 2026.

Abstract

To investigate the role of transcription factor AP-2γ (TFAP2C) in hypertensive endothelial dysfunction and elucidate the regulatory mechanism of the miR-3656/TFAP2C/SPRY4 signaling axis. Plasma TFAP2C levels were measured by ELISA in 91 hypertensive patients and 101 healthy controls. Human umbilical vein endothelial cells (HUVECs) and human aortic endothelial cells (HAECs) were subjected to TFAP2C overexpression or knockdown, followed by assessment of cell proliferation, migration, apoptosis, and tube formation. Bioinformatics prediction, ChIP-qPCR, dual-luciferase reporter assay, RT-qPCR, and western blot were used to identify Sprouty4 (SPRY4) as a direct transcriptional target of TFAP2C. Rescue experiments confirmed the mediating role of SPRY4 and the hierarchical relationship of the miR-3656/TFAP2C/SPRY4 axis. TFAP2C levels were significantly lower in hypertensive patients than in healthy controls (7.40 ± 6.28 vs. 10.04 ± 5.90, p = 0.003) and correlated negatively with blood pressure. TFAP2C overexpression significantly enhanced endothelial proliferation, migration, and tube formation while inhibiting apoptosis, whereas TFAP2C knockdown produced the opposite effects (p < 0.05). SPRY4 was identified as a direct transcriptional target of TFAP2C. Rescue experiments demonstrated that SPRY4 overexpression partially reversed TFAP2C knockdown-induced endothelial dysfunction. Furthermore, miR-3656 negatively regulated the TFAP2C/SPRY4 axis, and SPRY4 overexpression alleviated miR-3656-induced impairment of endothelial function. TFAP2C is downregulated in hypertensive patients and exerts protective effects against endothelial dysfunction by transcriptionally activating SPRY4. The miR-3656/TFAP2C/SPRY4 axis represents a novel regulatory cascade in endothelial dysfunction. TFAP2C may serve as a potential circulating marker associated with endothelial dysfunction in hypertension.

PMID:
43023991
Bibliographic data and abstract were imported from PubMed on 13 Nov 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.