Exp Clin Endocrinol Diabetes 2023; 131(03): 162-172
DOI: 10.1055/a-1989-1918
Article

E2F2 Promotes Wound Healing of Diabetic Foot Ulcer by Regulating CDCA7L Transcription

Meimei Xiao
1   Department of Hand and Foot Microsurgery, The Affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang, Hunan, P.R. China
,
Jiusong Wang
1   Department of Hand and Foot Microsurgery, The Affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang, Hunan, P.R. China
,
Yanming Chen
1   Department of Hand and Foot Microsurgery, The Affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang, Hunan, P.R. China
› Author Affiliations
Funding This research was funded by grants from the Hunan Provincial Health Commission (Grant No. 20201906), the Hunan Provincial Health and Family Planning Commission (Grant No. A2017018), and the Hunan Provincial Clinical Medical Research Center (Grant No. 2021SK4030).

Abstract

Objective The E2F2 transcription factor can accelerate cell proliferation and wound healing. However, its mechanism of action in a diabetic foot ulcer (DFU) remains unclear. Therefore, this study explores the influence of E2F2 on wound healing in DFU by examining cell division cycle-associated 7-like (CDCA7L) expression.

Methods CDCA7L and E2F2 expression in DFU tissues were analyzed with databases. CDCA7L and E2F2 expression were altered in human umbilical vein endothelial cells (HUVECs) and spontaneously transformed human keratinocyte cell culture (HaCaT) cells. Cell viability, migration, colony formation, and angiogenesis were evaluated. Binding of E2F2 to the CDCA7L promoter was examined. Subsequently, a diabetes mellitus (DM) mouse model was established and treated with full-thickness excision followed by CDCA7L overexpression. Wound healing in these mice was observed and recorded, and vascular endothelial growth factor receptor 2 (VEGFR2) and hematopoietic progenitor cell antigen CD34 (CD34) expression were determined. E2F2 and CDCA7L expression levels in cells and mice were evaluated. The expression of growth factors was tested.

Results CDCA7L expression was downregulated in DFU tissues and wound tissues from DM mice. Mechanistically, E2F2 bound to the CDCA7L promoter to upregulate CDCA7L expression. E2F2 overexpression enhanced viability, migration, and growth factor expression in HaCaT cells and HUVECs, and augmented HUVEC angiogenesis and HaCaT cell proliferation, which was nullified by silencing CDCA7L. In DM mice, CDCA7L overexpression facilitated wound healing and elevated the expression level of growth factors.

Conclusions E2F2 facilitated cell proliferation and migration and fostered wound healing in DFU cells through binding to the CDCA7L promoter.



Publication History

Received: 28 July 2022
Received: 17 November 2022

Accepted: 17 November 2022

Article published online:
09 March 2023

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