Chinese Journal of Tissue Engineering Research ›› 2025, Vol. 29 ›› Issue (25): 5396-5402.doi: 10.12307/2025.516

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Angiopoietin-like protein 4 affects progression of diabetic foot by regulating fibroblast and endothelial cell functions

Song Qinghong1, Wu Nan1, Shi Yan1, Cui Hongyu1, Liu Fei1, Liu Hanchong1, Zhou Ning1, Yao Bin2   

  1. 1Vascular Disease Diagnosis and Treatment Center, Tianjin Union Medical Center, Tianjin 300121, China; 2Tianjin University, Tianjin 300072, China
  • Received:2024-04-02 Accepted:2024-06-03 Online:2025-09-08 Published:2024-12-26
  • Contact: Yao Bin, MD, Associate professor, Tianjin University, Tianjin 300072, China
  • About author:Song Qinghong, MD, Associate chief physician, Vascular Disease Diagnosis and Treatment Center, Tianjin Union Medical Center, Tianjin 300121, China
  • Supported by:
    National Key Research & Development Project, No. 2022YFC2403100 (to YB); Science and Technology Project of Tianjin Health Commission, No. ZC20112 (to SQH)

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Abstract: BACKGROUND: Studies have shown that vascular factors have an important impact on the occurrence of diabetic foot.
OBJECTIVE: To investigate the important role of angiopoietin-like protein 4 in the formation of diabetic foot.
METHODS: (1) Bioinformatics analysis was performed on the gene expression profile data of diabetic foot patients to find the key genes. The skin samples of diabetic foot patients and healthy people were collected for hematoxylin-eosin staining, immunohistochemical staining, and qRT-PCR experiments to detect the expression of angiopoietin-like protein 4. (2) The immortalized human skin fibroblast cell line and primary human umbilical vein endothelial cells were cultured. The two kinds of cells were divided into control group and exogenous angiopoietin-like protein 4 supplemented group. The migration ability and proliferation ability of fibroblasts were detected by scratch assay and CCK-8 assay. The proliferation ability of endothelial cells was detected by Ki67 assay.
RESULTS AND CONCLUSION: (1) Bioinformatics analysis results showed that the down-regulation of angiopoietin-like protein 4 gene might be the key gene leading to the formation of diabetic foot. (2) Hematoxylin-eosin staining exhibited that compared with normal skin, angiopoietin-like protein 4 was weakly expressed in diabetic foot skin, and the mRNA level was decreased (P < 0.01). (3) Scratch assay results demonstrated that compared with the control group, fibroblast migration ability was significantly enhanced in the angiopoietin-like protein 4 group. CCK-8 assay showed that the absorbance value of fibroblasts in the angiopoietin-like protein 4 group was higher than that of the control group at 24 and 48 hours (P < 0.01, P < 0.001). It is suggested that angiopoietin-like protein 4 can enhance the migration and proliferation of fibroblasts. (4) Ki67 assay results demonstrated that the number of Ki67 positive cells in the angiopoietin-like protein 4 group was significantly more than that in the control group. CCK-8 assay results showed that the absorbance value of endothelial cells in the angiopoietin-like protein 4 group was higher than that of the control group at 24 and 48 hours (P < 0.05, P < 0.001). (5) All findings suggest that angiopoietin-like protein 4 can enhance the proliferation of endothelial cells treated with high glucose.

Key words: angiopoietin-like protein 4, fibroblast, vascular endothelial cell, diabetic foot, bioinformatics analysis

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