CXXC5 function blockade promotes diabetic wound healing through stimulating fibroblast and vascular endothelial cell activation.

IF 8.2 2区生物学 Q1 CELL BIOLOGY

Cell Communication and Signaling Pub Date : 2025-02-25 DOI:10.1186/s12964-025-02097-z

Yutong Chen, Xiaofeng Ding, Zhouji Ma, Shuai Shao, Heyan Huang, Yumeng Huang, Beizhi Wang, Hao Zhang, Qian Tan

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引用次数: 0

Abstract

Background: Extracellular matrix (ECM) and angiogenesis are critical controls of wound regeneration, and their dysfunction delays diabetes recovery. CXXC5 belongs to the CXXC protein family that can regulate the function of human dermal fibroblasts (HDFs) and human umbilical vein endothelial cells (HUVECs); However, awareness of its functional role remains limited.

Methods: Mice were divided into control (CON), diabetic (DM), diabetic + KY19382 (DM + KY19382), and diabetic + vehicle (DM + Vehicle) groups. HDFs and HUVECs were stimulated under different CXXC5 conditions and mice were treated with KY19382, followed by the application of assays including Western blotting (WB), immunofluorescence (IF) and quantitative reverse transcription-PCR (qRT-PCR) to assess wound healing and molecular signaling.

Results: Mice in DM had fewer blood vessels, a slower wound healing rate, and more disrupted collagen than CON. Application of KY19382 improved these conditions, which promoted fibroblast activation and vascularization in high glucose environments and DM. Mechanistically, blocking CXXC5 promotes Wnt/β-catenin-mediated stabilization by reducing the binding of the deterrent factor CTBP1 to β-catenin, which induces dermal fibroblast activation and facilitates HUVECs tube formation and migration via VEGFA/VEGFR2 and NFκB signaling pathways. KY19382 promotes HUVECs activation by blocking CTBP1 transcription to activate the NFκB signaling pathway, thus wound re-vascularization.

Conclusion: CXXC5 is an essential regulatory factor of wound healing and a prospective therapeutic target for treating chronic wound damage in diabetes.

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来源期刊

Cell Communication and Signaling CELL BIOLOGY-

CiteScore

11.00

自引率

0.00%

发文量

180

期刊介绍： Cell Communication and Signaling (CCS) is a peer-reviewed, open-access scientific journal that focuses on cellular signaling pathways in both normal and pathological conditions. It publishes original research, reviews, and commentaries, welcoming studies that utilize molecular, morphological, biochemical, structural, and cell biology approaches. CCS also encourages interdisciplinary work and innovative models, including in silico, in vitro, and in vivo approaches, to facilitate investigations of cell signaling pathways, networks, and behavior. Starting from January 2019, CCS is proud to announce its affiliation with the International Cell Death Society. The journal now encourages submissions covering all aspects of cell death, including apoptotic and non-apoptotic mechanisms, cell death in model systems, autophagy, clearance of dying cells, and the immunological and pathological consequences of dying cells in the tissue microenvironment.