Evidence mapPaperPMID 40143429Full record

ArticleChinese medical journal2025

S100A9 as a promising therapeutic target for diabetic foot ulcers.

Renhui Wan, Shuo Fang, Xingxing Zhang, Weiyi Zhou, Xiaoyan Bi, Le Yuan, Qian Lv, Yan Song, Wei Tang, Yongquan Shi and 1 more

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Article in Chinese medical journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
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  3. The mechanism and application ofFrontiers in endocrinology · 2025
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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Renhui WanDepartment of Endocrinology, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
Shuo FangDepartment of Plastics, Changhai Hospital, Naval Medical University, Shanghai 200433, China.
Xingxing ZhangDepartment of Endocrinology, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
Weiyi ZhouDepartment of Endocrinology, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
Xiaoyan BiDepartment of Endocrinology, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
Le YuanDepartment of Endocrinology, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
Qian LvDepartment of Endocrinology, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
Yan SongDepartment of Endocrinology, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
Wei TangDepartment of Endocrinology, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
Yongquan ShiDepartment of Endocrinology, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
Tuo LiDepartment of Endocrinology, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDiabetic foot is a complex condition with high incidence, recurrence, mortality, and disability rates. Current treatments for diabetic foot ulcers are often insufficient. This study was conducted to identify potential therapeutic targets for diabetic foot.

methodsDatasets related to diabetic foot and diabetic skin were retrieved from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using R software. Enrichment analysis was conducted to screen for critical gene functions and pathways. A protein interaction network was constructed to identify node genes corresponding to key proteins. The DEGs and node genes were overlapped to pinpoint target genes. Plasma and chronic ulcer samples from diabetic and non-diabetic individuals were collected. Western blotting, immunohistochemistry, and enzyme-linked immunosorbent assays were performed to verify the S100 calcium binding protein A9 (S100A9), inflammatory cytokine, and related pathway protein levels. Hematoxylin and eosin staining was used to measure epidermal layer thickness.

resultsIn total, 283 common DEGs and 42 node genes in diabetic foot ulcers were identified. Forty-three genes were differentially expressed in the skin of diabetic and non-diabetic individuals. The overlapping of the most significant DEGs and node genes led to the identification of S100A9 as a target gene. The S100A9 level was significantly higher in diabetic than in non-diabetic plasma (178.40 ± 44.65 ng/mL vs. 40.84 ± 18.86 ng/mL) and in chronic ulcers, and the wound healing time correlated positively with the plasma S100A9 level. The levels of inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1, and IL-6) and related pathway proteins (phospho-extracellular signal regulated kinase [ERK], phospho-p38, phospho-p65, and p-protein kinase B [Akt]) were also elevated. The epidermal layer was notably thinner in chronic diabetic ulcers than in non-diabetic skin (24.17 ± 25.60 μm vs. 412.00 ± 181.60 μm).

conclusionsS100A9 was significantly upregulated in diabetic foot and was associated with prolonged wound healing. S100A9 may impair diabetic wound healing by disrupting local inflammatory responses and skin re-epithelialization.

Indexed as

Calgranulin BDiabetic FootAnimalsComputational BiologyDatasets as TopicHumansImmunohistochemistryMiceMice, Inbred C57BLProtein Interaction MapsCalgranulin BS100A9 protein, humanBioinformatical analysisDiabetic foot ulcerInflammatory factorS100A9Therapeutic target

Identifiers

PMID40143429
PMCPMC12037093

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.