Integrated insights into gene expression dynamics and transcription factor roles in diabetic and diabetic-infectious wound healing using rat model

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-02-25 DOI:10.1016/j.lfs.2025.123508

Vikash Sharma , Jitender Singh , Yash Kumar , Ashish Kumar , Kumar Venkatesan , Monalisa Mukherjee , Arun K. Sharma

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引用次数: 0

Abstract

Background

Diabetic or diabetic infectious wounds pose a global challenge, marked by delayed healing and high amputation/mortality rates. This study of participating transcriptomes and their regulators unveils critical alterations.

Methods

Transcriptome data from GEO analyzed DEGs in diabetic foot ulcers vs. controls using RNA-Seq, limma, STRINGdb, Cytoscape, and clusterProfiler for PPI networks and functional enrichment. TRRUST database was used to predict transcriptional factors (TFs). Adverse molecular pathology in different models of wounds (non-diabetic, acute diabetic, diabetic infectious wounds) was validated by RT-PCR, Western blotting, oxidative stress markers, cytokines, and histological analysis.

Results

RNA-Seq dataset ‘GSE199939’ was analyzed after normalization to identify DEGs (total 47 DEG, 31 upregulated, 16 downregulated) in diabetic wound healing using limma. PPI networks revealed seven hub genes which were further processed for functional enrichment and highlighted oxidative stress, ECM remodeling, AGE-RAGE, and IL-17 signaling in diabetic wound pathology. Additionally, 17 key TFs were identified as hub gene regulators. The healing rate was significantly impaired in diabetic wounds, with delayed contraction, elevated pro-inflammatory cytokines, oxidative stress, reduced anti-inflammatory cytokines, antioxidants, angiogenesis, collagen deposition, and re-epithelialization. Further, RT-PCR and Western blot analysis validated the expression of target genes including the overexpression of HSPA1B, FOS, and down-expression of SOD2, COL1A1, and CCL2, whereas TFs including upregulation of RELA, NFKB1, STAT3, and downregulation of SP1 and JUN in diabetic and diabetic infectious wounds.

Conclusion

Molecular analyses reveal disrupted oxidative stress, ECM remodeling, and inflammatory signaling in diabetic and diabetic infectious, emphasizing impaired healing dynamics and identifying therapeutic targets.

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.