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10.3390/cells11193126
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Article

HOCI Probe CPP Induces the Differentiation of Human Dermal Fibroblasts into Vascular Endothelial Cells through PHD2/HIF-1α/HEY1 Signaling Pathway

by
Xiaoling Cui
1,
Jie Wen
2,
Nan Li
1,
Xuxiao Hao
1,
Shangli Zhang
1,
Baoxiang Zhao
3,
Xunwei Wu
4,5,* and
Junying Miao
1,6,*
1
Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Qingdao 266237, China
2
School of Stomatology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, China
3
Institute of Organic Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China
4
Engineering Laboratory for Biomaterials and Tissue Regeneration, Ningbo Stomatology Hospital, Ningbo 315040, China
5
Savaid Stomatology School, Hangzhou Medical College, Hangzhou 310058, China
6
The Key Laboratory of Cardiovascular Remodeling and Function Research, Shandong University Qilu Hospital, Chinese Ministry of Education and Chinese Ministry of Health, Jinan 250012, China
*
Authors to whom correspondence should be addressed.
Cells 2022, 11(19), 3126; https://doi.org/10.3390/cells11193126
Submission received: 18 August 2022 / Revised: 26 September 2022 / Accepted: 1 October 2022 / Published: 4 October 2022
(This article belongs to the Section Cell Signaling)
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Abstract

Human dermal fibroblasts (HDFs) have the potential to differentiate into endothelial cells (VECs). In our previous research, we reported that a hypochlorous acid (HOCl) probe CPP efficiently induced the differentiation of HDFs into VECs, however, the mechanism of differentiation was not clear. As an HOCI probe, CPP binds HOCI to modulate its effects. In this study, through Western blotting, qPCR, and PHD2 enzyme activity assay, we found that CPP inhibited the enzyme activity of prolyl-4-hydroxylase 2 (PHD2), thereby stabilizing HIF-1α. To further clarify the mechanism by which CPP inhibits PHD2 enzyme activity, we constructed plasmids, and found that CPP inhibited PHD2 activity to increase the HIF-1α level through the modulation of PHD2 at Cys302 by HOCl in HDFs. Furthermore, RNA-seq experiments showed that CPP could induce the expression of HEY1, which is not only a target gene regulated by HIF1α, but also a key transcription factor for VECs. We used siRNA transfection and in vivo experiments to confirm that CPP could induce HDFs to differentiate into VECs by HEY1. In summary, we identified a new inhibitor of PHD2, demonstrated the new role of HOCl in cell differentiation, and elucidated the mechanism by which HOCl probe CPP induced the differentiation of HDFs into VECs.
Keywords: differentiation; human dermal fibroblasts; vascular endothelial cells; hypochlorous acid probe; PHD2/HIF-1α/HEY1 signal pathway differentiation; human dermal fibroblasts; vascular endothelial cells; hypochlorous acid probe; PHD2/HIF-1α/HEY1 signal pathway

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MDPI and ACS Style

Cui, X.; Wen, J.; Li, N.; Hao, X.; Zhang, S.; Zhao, B.; Wu, X.; Miao, J. HOCI Probe CPP Induces the Differentiation of Human Dermal Fibroblasts into Vascular Endothelial Cells through PHD2/HIF-1α/HEY1 Signaling Pathway. Cells 2022, 11, 3126. https://doi.org/10.3390/cells11193126

AMA Style

Cui X, Wen J, Li N, Hao X, Zhang S, Zhao B, Wu X, Miao J. HOCI Probe CPP Induces the Differentiation of Human Dermal Fibroblasts into Vascular Endothelial Cells through PHD2/HIF-1α/HEY1 Signaling Pathway. Cells. 2022; 11(19):3126. https://doi.org/10.3390/cells11193126

Chicago/Turabian Style

Cui, Xiaoling, Jie Wen, Nan Li, Xuxiao Hao, Shangli Zhang, Baoxiang Zhao, Xunwei Wu, and Junying Miao. 2022. "HOCI Probe CPP Induces the Differentiation of Human Dermal Fibroblasts into Vascular Endothelial Cells through PHD2/HIF-1α/HEY1 Signaling Pathway" Cells 11, no. 19: 3126. https://doi.org/10.3390/cells11193126

APA Style

Cui, X., Wen, J., Li, N., Hao, X., Zhang, S., Zhao, B., Wu, X., & Miao, J. (2022). HOCI Probe CPP Induces the Differentiation of Human Dermal Fibroblasts into Vascular Endothelial Cells through PHD2/HIF-1α/HEY1 Signaling Pathway. Cells, 11(19), 3126. https://doi.org/10.3390/cells11193126

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