{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T11:24:22Z","timestamp":1784201062536,"version":"3.55.0"},"reference-count":47,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T00:00:00Z","timestamp":1765670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"GMS Capitals LLC","award":["25270C"],"award-info":[{"award-number":["25270C"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diabetic foot ulcers (DFUs) are a leading cause of morbidity worldwide along with the risk of other chronic health issues. Hyperglycemia has been shown to alter immune regulation at the wound site and potentially contributes to non-healing DFUs. However, the effects of hyperglycemia on the expression of mediators of inflammation and angiogenesis (CD36), immune regulation (TLR-7 and CD69), and inflammation\/tissue repair (CD274) regarding wound healing are unknown. This study aims to investigate the effects of hyperglycemia on the gene and protein expression of CD36, CD69, CD274, and TLR-7 during wound healing using a rat model of induced diabetes. The expression of these mediators was examined using cutaneous tissues from rat models of diabetes with cutaneous wounds. Skin samples (n = 7 each, control and healed) from the control and diabetic rats were analyzed using hematoxylin and eosin as well as trichrome staining, immunohistochemistry, and PCR. In vitro studies were conducted using rat fibroblasts. Hyperglycemia significantly increases the expression of CD36, CD69, and CD274 and increases TLR-7 expression but not significantly in diabetic tissues compared to control tissues. In vitro studies corroborate the findings in tissues. The modulation of these mediators by hyperglycemia suggests their probable role in delayed wound healing, and these mediators may be potential therapeutic targets to promote wound healing in DFUs.<\/jats:p>","DOI":"10.3390\/ijms262412032","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T09:36:39Z","timestamp":1765791399000},"page":"12032","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hyperglycemia Induced in Sprague\u2013Dawley Rats Modulates the Expression of CD36 and CD69 During Wound Healing"],"prefix":"10.3390","volume":"26","author":[{"given":"Vy","family":"Ho","sequence":"first","affiliation":[{"name":"College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommy","family":"Tran","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaylan","family":"Patel","sequence":"additional","affiliation":[{"name":"College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7306-4485","authenticated-orcid":false,"given":"Betelhem","family":"Teshome","sequence":"additional","affiliation":[{"name":"Department of Translational Research, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6286-2341","authenticated-orcid":false,"given":"Vikrant","family":"Rai","sequence":"additional","affiliation":[{"name":"Department of Translational Research, Western University of Health Sciences, Pomona, CA 91766, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S151","DOI":"10.2337\/dc09-S301","article-title":"Defining and characterizing the progression of type 2 diabetes","volume":"32","author":"Fonseca","year":"2009","journal-title":"Diabetes Care"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Okano, J., Kojima, H., Katagi, M., Nakagawa, T., Nakae, Y., Terashima, T., Kurakane, T., Kubota, M., Maegawa, H., and Udagawa, J. 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