{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:49:11Z","timestamp":1787017751341,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":104,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Diabetic foot ulcer (DFU) is a serious complication of diabetes. This study aims to screen DFU\u2013associated immune\u2010related genes (IRGs) and investigate their potential functional mechanisms and clinical relevance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Based on the GSE80178 dataset, the differentially expressed genes (DEGs) between DFU and diabetic foot skin (DFS) were screened out and cross\u2010linked with IRGs to obtain differentially expressed IRGs (DE\u2010IRGs). Functional enrichment analysis was conducted using the \u201cclusterProfiler\u201d R package. The protein\u2013protein interaction (PPI) network was constructed using the STRING platform, and the core genes were identified based on topological analysis. The expression and diagnostic efficacy of core genes were verified using external datasets (GSE199939 and GSE134431). Immune cell infiltration analysis was performed using CIBERSORT algorithm. The candidate drugs were predicted through the L1000FWD database and molecular docking was carried out with Autodock Vina. The function of the core gene and its molecular mechanism were verified by constructing a high glucose (HG)\u2013induced HaCaT cell injury model in vitro.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 108 DE\u2010IRGs were screened out, including 48 upregulated genes and 60 downregulated genes. These genes were significantly enriched in the cytokine\u2013cytokine receptor interaction, phosphoinositol 3\u2010kinase (PI3K)\u2013protein kinase B (Akt) and mitogen\u2010activated protein kinase (MAPK) signaling pathways. Fibroblast growth factor receptor (FGFR) 2 was identified as the core gene, and its expression was significantly downregulated in DFU, with high diagnostic value (area under the curve [AUC]\u2009&gt;0.95). The expression of FGFR2 was correlated with the infiltration levels of various immune cells. QL\u2010XI\u201092, reversine, BRD\u2010K67414432, LY294002, and neratinib had high binding affinity with the FGFR2 protein. HG significantly reduced the expression of FGFR2 in HaCaT cells, inhibited proliferation and migration, and promoted apoptosis and the secretion of tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), interleukin (IL)\u20101\u03b2 and IL\u20106; overexpression of FGFR2 reversed the above\u2010mentioned phenomena and activated the PI3K\/Akt and p38 MAPK pathways. The protective effect of FGFR2 could be reversed by LY294002 (an inhibitor of PI3K\/Akt pathway) or SB202190 (a p38 MAPK inhibitor).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>FGFR2 is lowly expressed in DFU and can exert a protective effect by activating the PI3K\/Akt pathway. It is a candidate diagnostic biomarker and potential therapeutic target for DFU.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/mi\/3260549","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T11:54:27Z","timestamp":1776254067000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["FGFR2 is a Candidate Immune\u2010Associated Marker of Diabetic Foot Ulcer That Promotes Keratinocyte Function by Activating the PI3K\/Akt and MAPK Pathways"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3447-9996","authenticated-orcid":false,"given":"Hailan","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1857-2245","authenticated-orcid":false,"given":"Hongfei","family":"Sang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1511-449X","authenticated-orcid":false,"given":"Yi","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5708-2462","authenticated-orcid":false,"given":"Jie","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7904-2726","authenticated-orcid":false,"given":"Chuang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1803-6932","authenticated-orcid":false,"given":"Fengrui","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"e_1_2_12_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.3776"},{"key":"e_1_2_12_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2025.118498"},{"key":"e_1_2_12_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.10578"},{"key":"e_1_2_12_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/wrr.70085"},{"key":"e_1_2_12_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/iwj.14017"},{"key":"e_1_2_12_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/1753-0407.13372"},{"key":"e_1_2_12_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-024-10038-2"},{"key":"e_1_2_12_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222111552"},{"key":"e_1_2_12_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13051076"},{"key":"e_1_2_12_10_2","doi-asserted-by":"crossref","DOI":"10.4103\/jrms.jrms_573_24","article-title":"Microenvironment of Diabetic Foot Ulcers: Implications for Healing and Therapeutic Strategies","volume":"30","author":"Wang J.","year":"2025","journal-title":"Journal of Research in Medical Sciences;"},{"key":"e_1_2_12_11_2","doi-asserted-by":"publisher","DOI":"10.4239\/wjd.v15.i12.2384"},{"key":"e_1_2_12_12_2","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14102065"},{"key":"e_1_2_12_13_2","doi-asserted-by":"publisher","DOI":"10.1080\/10641963.2023.2208777"},{"key":"e_1_2_12_14_2","doi-asserted-by":"publisher","DOI":"10.1080\/10985549.2024.2399766"},{"key":"e_1_2_12_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2023.08.013"},{"key":"e_1_2_12_16_2","doi-asserted-by":"crossref","first-page":"5690","DOI":"10.1242\/jcs.108167","article-title":"FGF Receptors 1 and 2 are Key Regulators of Keratinocyte Migration In Vitro and in Wounded Skin","volume":"125","author":"Meyer M.","year":"2012","journal-title":"Journal of Cell Science"},{"key":"e_1_2_12_17_2","doi-asserted-by":"publisher","DOI":"10.2741\/2277"},{"key":"e_1_2_12_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-025-03012-5"},{"key":"e_1_2_12_19_2","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2105-13-335","article-title":"Unlocking the Potential of Publicly Available Microarray Data Using inSilicoDb and in SilicoMerging R\/Bioconductor Packages","volume":"13","author":"Taminau J.","year":"2012","journal-title":"BMC Bioinformatics"},{"key":"e_1_2_12_20_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1561179"},{"key":"e_1_2_12_21_2","doi-asserted-by":"publisher","DOI":"10.12998\/wjcc.v11.i8.1684"},{"key":"e_1_2_12_22_2","doi-asserted-by":"crossref","DOI":"10.3389\/fendo.2021.744868","article-title":"Fibroblast Growth Factor in Diabetic Foot Ulcer: Progress and Therapeutic Prospects","volume":"12","author":"Liu Y.","year":"2021","journal-title":"Frontiers in Endocrinology"},{"key":"e_1_2_12_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e24598"},{"key":"e_1_2_12_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.14389"},{"key":"e_1_2_12_25_2","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm_00000132"},{"key":"e_1_2_12_26_2","doi-asserted-by":"publisher","DOI":"10.1159\/000493287"},{"key":"e_1_2_12_27_2","doi-asserted-by":"publisher","DOI":"10.3390\/ph16010066"},{"key":"e_1_2_12_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.14327"},{"key":"e_1_2_12_29_2","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S424847"},{"key":"e_1_2_12_30_2","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S359759"},{"key":"e_1_2_12_31_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-025-04141-8"},{"key":"e_1_2_12_32_2","doi-asserted-by":"crossref","first-page":"8783","DOI":"10.2147\/IJN.S531396","article-title":"New Strategies for the Treatment of Diabetic Foot Ulcers Using Nanoenzymes: Frontline Advances in Anti-Infection, Immune Regulation, and Microenvironment Improvement","volume":"20","author":"Jia S.","year":"2025","journal-title":"International Journal of Nanomedicine"},{"key":"e_1_2_12_33_2","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S442388"},{"key":"e_1_2_12_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/1753-0407.70166"},{"key":"e_1_2_12_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmz095"},{"key":"e_1_2_12_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-025-00850-8"},{"key":"e_1_2_12_37_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1801199"},{"key":"e_1_2_12_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-59318-9"},{"key":"e_1_2_12_39_2","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.10637"},{"key":"e_1_2_12_40_2","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbo.2024.100601","article-title":"Reversine Inhibits Proliferation and Induces Apoptosis of Human Osteosarcoma Cells Through Targeting MEK1","volume":"46","author":"Chen X.","year":"2024","journal-title":"Journal of Bone Oncology;"},{"key":"e_1_2_12_41_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-023-00736-0"},{"key":"e_1_2_12_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12880-5"}],"container-title":["Mediators of Inflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/mi\/3260549","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/mi\/3260549","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/mi\/3260549","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T11:54:29Z","timestamp":1776254069000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/mi\/3260549"}},"subtitle":[],"editor":[{"given":"Alessandro","family":"Medoro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":42,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/mi\/3260549"],"URL":"https:\/\/doi.org\/10.1155\/mi\/3260549","archive":["Portico"],"relation":{},"ISSN":["0962-9351","1466-1861"],"issn-type":[{"value":"0962-9351","type":"print"},{"value":"1466-1861","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-12-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-15","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"3260549"}}