Comprehensive transcriptomic profiling reveals tissue-specific molecular signatures and dysregulated pathways in human diabetic foot ulcers

	Comprehensive transcriptomic profiling reveals tissue-specific molecular signatures and dysregulated pathways in human diabetic foot ulcers
	Hu, GR; Nisar, A; Khan, S; Li, W; Zhu, EF; Cui, HL; Zhang, GQ; He, YH; Sun, H
	2025
发表期刊	Front. Endocrinol.
ISSN	1664-2392
卷号	16
摘要	Background Diabetic foot ulcers (DFUs) are a severe complication of diabetes mellitus characterized by impaired wound healing, chronic inflammation, and tissue degeneration. We sought to identify tissue specific molecular drivers of DFU pathogenesis across skin, adipose, and muscle compartments.Methods High throughput RNA sequencing was performed on skin, adipose, and muscle tissues from DFU patients and non-ulcerated diabetic controls. Differential expression analyses and pathway enrichment were conducted to delineate common and compartment-specific transcriptional changes.Results All DFU tissues exhibited a conserved upregulation of immune activation genes-including chemokines (CXCL1-8), cytokines (IL1B, IL6), and NF-kappa B pathway components-alongside downregulation of metabolic regulators (PPARG, ADIPOQ), oxidative phosphorylation genes (SDHA, NDUFS2), and insulin signaling factors (IRS1, AKT2). Skin showed increased keratinocyte proliferation and senescence markers (KRT16, FOXM1); adipose tissue revealed adipocyte dedifferentiation and elevated matrix protease activity (MMP9); and muscle displayed fibrotic remodeling and mitochondrial suppression (COL1A1, NDUFS7). Enrichment analyses implicated IL17 signaling, PPAR pathways, and cellular senescence as central disrupted processes.Conclusion DFUs are driven by a dual pathology of inflammatory amplification and metabolic shutdown, overlaid with distinct tissue-specific alterations. Key targets such as chemokine signaling, PPAR-mediated metabolism, and senescence factors emerge as promising candidates for precision therapies aimed at restoring inflammatory-metabolic balance and enhancing wound healing.
收录类别	SCIE
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/15054
专题	科研部门_神经系统疾病（罗雄剑）
推荐引用方式 GB/T 7714	Hu, GR,Nisar, A,Khan, S,et al. Comprehensive transcriptomic profiling reveals tissue-specific molecular signatures and dysregulated pathways in human diabetic foot ulcers[J]. Front. Endocrinol.,2025,16.
APA	Hu, GR.,Nisar, A.,Khan, S.,Li, W.,Zhu, EF.,...&Sun, H.(2025).Comprehensive transcriptomic profiling reveals tissue-specific molecular signatures and dysregulated pathways in human diabetic foot ulcers.Front. Endocrinol.,16.
MLA	Hu, GR,et al."Comprehensive transcriptomic profiling reveals tissue-specific molecular signatures and dysregulated pathways in human diabetic foot ulcers".Front. Endocrinol. 16(2025).

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
2026071322.pdf（6178KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文