title: Detection of RAGE expression and its application to diabetic wound age estimation.
abstract: With the prevalence of diabetes, it is becoming important to analyze the diabetic wound age in forensic practice. The present study investigated the time-dependent expression of receptor for advanced glycation end products (RAGE) during diabetic wound healing in mice and its applicability to wound age determination by immunohistochemistry, double immunofluorescence, and Western blotting. After an incision was created in genetically diabetic db/db mice and control mice, mice were killed at posttraumatic intervals ranging from 6 h to 14 days, followed by the sampling of wound margin. Compared with control mice, diabetic mice showed the delayed wound healing. In control and diabetic wound specimens, RAGE immunoreactivity was observed in a small number of polymorphonuclear cells (PMNs), a number of macrophages, and fibroblasts. Morphometrically, the positive ratios of RAGE in macrophages or fibroblasts considerably increased in diabetic wounds during late repair, which exceeded 60% at 7 and 10 days post-injury. There were no control wound specimens to show a ratio of >60% in macrophages or fibroblasts. By Western blotting analysis, the ratios of RAGE to GAPDH were >1.4 in all diabetic wound samples from 7 to 10 days post-injury, which were >1.8 at 10 days after injury. By comparison, no control wound specimens indicated a ratio of >1.4. In conclusion, the expression of RAGE is upregulated and temporally distributed in macrophages and fibroblasts during diabetic wound healing, which might be closely involved in prolonged inflammation and deficient healing. Moreover, RAGE is promising as a useful marker for diabetic wound age determination.
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Science, Wenzhou Medical University, Higher Education District, Wenzhou, 325035, Zhejiang Province, People's Republic of China.|Forensic Center, Wenzhou Medical University, Wenzhou, 325027, Zhejiang Province, People's Republic of China.
authors.forename: Xin-Yi
authors.initials: XY
authors.lastname: Ji
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Science, Wenzhou Medical University, Higher Education District, Wenzhou, 325035, Zhejiang Province, People's Republic of China.|Forensic Center, Wenzhou Medical University, Wenzhou, 325027, Zhejiang Province, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Science, Wenzhou Medical University, Higher Education District, Wenzhou, 325035, Zhejiang Province, People's Republic of China.|Forensic Center, Wenzhou Medical University, Wenzhou, 325027, Zhejiang Province, People's Republic of China.
authors.forename: Guang-Hua
authors.initials: GH
authors.lastname: Ye
authors.affiliation: Center of Basic Medical Experiment, School of Basic Medical Science, Wenzhou Medical University, Higher Education District, Wenzhou, 325035, Zhejiang Province, People's Republic of China.
authors.forename: Miao-Wu
authors.initials: MW
authors.lastname: Dong
authors.affiliation: Center of Basic Medical Experiment, School of Basic Medical Science, Wenzhou Medical University, Higher Education District, Wenzhou, 325035, Zhejiang Province, People's Republic of China.
authors.forename: Ke-Zhi
authors.initials: KZ
authors.lastname: Lin
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Science, Wenzhou Medical University, Higher Education District, Wenzhou, 325035, Zhejiang Province, People's Republic of China.|Forensic Center, Wenzhou Medical University, Wenzhou, 325027, Zhejiang Province, People's Republic of China.
authors.forename: Jun-Ge
authors.initials: JG
authors.lastname: Han
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Science, Wenzhou Medical University, Higher Education District, Wenzhou, 325035, Zhejiang Province, People's Republic of China.|Forensic Center, Wenzhou Medical University, Wenzhou, 325027, Zhejiang Province, People's Republic of China.
authors.forename: Xiang-Ping
authors.initials: XP
authors.lastname: Feng
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Science, Wenzhou Medical University, Higher Education District, Wenzhou, 325035, Zhejiang Province, People's Republic of China.|Forensic Center, Wenzhou Medical University, Wenzhou, 325027, Zhejiang Province, People's Republic of China.
authors.forename: Xing-Biao
authors.initials: XB
authors.lastname: Li
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Science, Wenzhou Medical University, Higher Education District, Wenzhou, 325035, Zhejiang Province, People's Republic of China. yls@wzmc.edu.cn.|Forensic Center, Wenzhou Medical University, Wenzhou, 325027, Zhejiang Province, People's Republic of China. yls@wzmc.edu.cn.
authors.forename: Lin-Sheng
authors.initials: LS
authors.lastname: Yu
authors.affiliation: Department of Forensic Medicine, School of Basic Medical Science, Wenzhou Medical University, Higher Education District, Wenzhou, 325035, Zhejiang Province, People's Republic of China. yyfan998@163.com.|Forensic Center, Wenzhou Medical University, Wenzhou, 325027, Zhejiang Province, People's Republic of China. yyfan998@163.com.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Fan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D008810:Mice, Inbred C57BL; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism*; D012867:Skin / Q000293:injuries* / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation; D014945:Wound Healing / Q000502:physiology*
chemical_list: C000593873:Ager protein, mouse; D015415:Biomarkers; D000067759:Receptor for Advanced Glycation End Products
keywords: Diabetic wound; Forensic pathology; RAGE; Wound age determination