{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:17:15Z","timestamp":1790425035216,"version":"4.1.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T00:00:00Z","timestamp":1673568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Diabetic foot ulcer (DFU) represents a highly-prevalent complication of diabetes mellitus (DM). Herein, the current study sought to identify the role of growth differentiation factor 10 (GDF-10) in wound healing in DFU <jats:italic>via<\/jats:italic> regulation of the transforming growth factor-beta 1 (TGF-\u03b21)\/Smad3 pathway.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>DM- and DFU-related microarray datasets GSE29221 and GSE134431 were firstly retrieved, and weighted gene co-expression network analysis (WGCNA) was carried out to construct a co-expression network affecting wound healing in DFU, followed by differential analysis. A protein-protein interaction (PPI) network of the DFU-related genes was subsequently constructed, and the core genes and signaling pathways in DFU were screened with the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional analyses. A DFU rat model was constructed for mechanism verification of the effect of GDF-10 on wound healing in DFU.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>WGCNA screened five co-expression modules, and the brown module was most closely-related to DM. Clustering analysis screened 4417 candidate genes, of which 175 differential genes were associated with wound healing, further involved in TGF-\u03b21\/Smad3 signaling pathway regulation of wound healing in DFU. The PPI network analysis predicted that GDF-10 might regulate the TGF-\u03b21\/Smad3 signaling pathway to participate in DFU development. Results of animal experimentation showed that the wound healing rates of NFU, DFU, DFU + GDF and GDF + SIS3 groups on the 22nd day were (87.66 \u00b1 6.80)%, (56.31 \u00b1 7.29)%, (71.64 \u00b1 9.43)% and (55.09 \u00b1 7.13)%, respectively. Besides, the expression of TGF-\u03b21 in NFU, DFU, DFU + GDF and GDF + SIS3 groups was 0.988 \u00b1 0.086, 0.297 \u00b1 0.036, 0.447 \u00b1 0.044, and 0.240 \u00b1 0.050, respectively, and that of Smad3 was 1.009 \u00b1 0.137, 0.145 \u00b1 0.017, 0.368 \u00b1 0.048, and 0.200 \u00b1 0.028, respectively. Specifically, GDF-10 exerted a significant diminishing effect on fasting blood glucose level, and promoted wound healing in DFU rats, in addition to up-regulation of VEGF, FGF, Ang-1, TGF-\u03b21, Smad3 and enhancement of IL-1b, IL-6, TNF-a and MMP-9, thereby promoting fibroblast proliferation, collagen deposition and angiogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our findings highlight that GDF-10 may promote angiogenesis by activating TGF-\u03b21\/Smad3 signaling, thereby promoting wound healing in DFU rats.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.1013018","type":"journal-article","created":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T05:05:42Z","timestamp":1673586342000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["Growth differentiation factor 10 induces angiogenesis to promote wound healing in rats with diabetic foot ulcers by activating TGF-\u03b21\/Smad3 signaling pathway"],"prefix":"10.3389","volume":"13","author":[{"given":"Qingsong","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinmei","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheqi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahui","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifeng","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"40","DOI":"10.2174\/1573399815666190307164119","article-title":"ADIE - nursing interventions of diabetic foot ulcer: An integrative review of the literature","volume":"16","author":"Subrata","year":"2019","journal-title":"Curr Diabetes Rev"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S268941","article-title":"Sesamol-loaded PLGA nanosuspension for accelerating wound healing in diabetic foot ulcer in rats","volume":"15","author":"Gourishetti","year":"2020","journal-title":"Int J Nanomed"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.31128\/AJGP-11-19-5161","article-title":"The diabetic foot ulcer","volume":"49","author":"Reardon","year":"2020","journal-title":"Aust J Gen Pract"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1177\/15347346211026819","article-title":"Therapeutic properties of honey for the management of wounds; is there a role in the armamentarium of diabetic foot ulcer treatment? 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