Open Access

Deciphering age‑related differences in wound healing: Insights from the interaction between endothelial cells and fibroblasts

  • Authors:
    • Jianjun Li
    • Dongzhen Zhu
    • Mengde Zhang
    • Zhao Li
    • Liting Liang
    • Yuyan Huang
    • Xu Guo
    • Yi Kong
    • Xiaobing Fu
    • Sha Huang
  • View Affiliations

  • Published online on: August 4, 2025     https://doi.org/10.3892/mmr.2025.13643
  • Article Number: 278
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Aging impairs wound healing, primarily because of alterations in cell phenotypes and interactions, particularly between endothelial cells (ECs) and fibroblasts (Fibs). The present study investigated the dynamics of EC‑Fib interactions in aged wounds using a mouse model and single‑cell transcriptomics, supplemented by CellChat analysis and functional validation using in vitro co‑culture systems. Aged mice exhibited markedly reduced wound healing efficiency and impaired angiogenesis when compared with younger mice, as indicated by hematoxylin and eosin and immunohistochemical staining. Single‑cell transcriptomic analysis revealed that the regeneration of ECs and Fibs was delayed in aged wounds. Furthermore, key genes involved in angiogenesis and tissue repair were downregulated, whereas those related to inflammation and aging were upregulated. Integrating CellChat analysis with in vitro co‑culture validation, it was found that the bidirectional communication between ECs and Fibs, predominantly mediated via the transforming growth factor β pathway, was markedly reduced in aged wounds. These findings underscored the critical role of disrupted cell‑cell communication in age‑related impaired wound healing, providing mechanistic evidence for potential therapeutic strategies to enhance wound healing in the elderly.
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October-2025
Volume 32 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Li J, Zhu D, Zhang M, Li Z, Liang L, Huang Y, Guo X, Kong Y, Fu X, Huang S, Huang S, et al: Deciphering age‑related differences in wound healing: Insights from the interaction between endothelial cells and fibroblasts. Mol Med Rep 32: 278, 2025.
APA
Li, J., Zhu, D., Zhang, M., Li, Z., Liang, L., Huang, Y. ... Huang, S. (2025). Deciphering age‑related differences in wound healing: Insights from the interaction between endothelial cells and fibroblasts. Molecular Medicine Reports, 32, 278. https://doi.org/10.3892/mmr.2025.13643
MLA
Li, J., Zhu, D., Zhang, M., Li, Z., Liang, L., Huang, Y., Guo, X., Kong, Y., Fu, X., Huang, S."Deciphering age‑related differences in wound healing: Insights from the interaction between endothelial cells and fibroblasts". Molecular Medicine Reports 32.4 (2025): 278.
Chicago
Li, J., Zhu, D., Zhang, M., Li, Z., Liang, L., Huang, Y., Guo, X., Kong, Y., Fu, X., Huang, S."Deciphering age‑related differences in wound healing: Insights from the interaction between endothelial cells and fibroblasts". Molecular Medicine Reports 32, no. 4 (2025): 278. https://doi.org/10.3892/mmr.2025.13643