Wu Siqi, Wang Yuetong, Duan Jingyi, Teng Ying, Wang Dali, Qi Fang
Department of Burns and Plastic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, China.
Front Physiol. 2024 Feb 16;15:1297810. doi: 10.3389/fphys.2024.1297810. eCollection 2024.
Diabetic foot ulcers (DFU) and cutaneous lupus erythematosus (CLE) are both diseases that can seriously affect a patient's quality of life and generate economic pressure in society. Symptomatically, both DLU and CLE exhibit delayed healing and excessive inflammation; however, there is little evidence to support a molecular and cellular connection between these two diseases. In this study, we investigated potential common characteristics between DFU and CLE at the molecular level to provide new insights into skin diseases and regeneration, and identify potential targets for the development of new therapies. The gene expression profiles of DFU and CLE were obtained from the Gene Expression Omnibus (GEO) database and used for analysis. A total of 41 common differentially expressed genes (DEGs), 16 upregulated genes and 25 downregulated genes, were identified between DFU and CLE. GO and KEGG analysis showed that abnormalities in epidermal cells and the activation of inflammatory factors were both involved in the occurrence and development of DFU and CLE. Protein-protein interaction network (PPI) and sub-module analysis identified enrichment in seven common key genes which is , , and . Based on these seven key genes, we further identified five miRNAs(has-mir-532-5p, has-mir-324-3p,has-mir-106a-5p,has-mir-20a-5p,has-mir-93-5p) and7 transcription factors including CEBPA, CEBPB, GLI1, EP30D, JUN,SP1, NFE2L2 as potential upstream molecules. Functional immune infiltration assays showed that these genes were related to immune cells. The CIBERSORT algorithm and Pearson method were used to determine the correlations between key genes and immune cells, and reverse key gene-immune cell correlations were found between DFU and CLE. Finally, the DGIbd database demonstrated that Paquinimod and Tasquinimod could be used to target S100A9 and Ribavirin could be used to target OASL. Our findings highlight common gene expression characteristics and signaling pathways between DFU and CLE, indicating a close association between these two diseases. This provides guidance for the development of targeted therapies and mutual interactions.
糖尿病足溃疡（DFU）和皮肤红斑狼疮（CLE）都是严重影响患者生活质量并给社会带来经济压力的疾病。从症状上看，DFU和CLE都表现出愈合延迟和炎症过度；然而，几乎没有证据支持这两种疾病之间存在分子和细胞层面的联系。在本研究中，我们在分子水平上研究了DFU和CLE之间潜在的共同特征，以提供对皮肤疾病和再生的新见解，并确定新疗法开发的潜在靶点。从基因表达综合数据库（GEO）中获取DFU和CLE的基因表达谱并进行分析。在DFU和CLE之间共鉴定出41个共同的差异表达基因（DEG），其中16个上调基因和25个下调基因。基因本体（GO）和京都基因与基因组百科全书（KEGG）分析表明，表皮细胞异常和炎症因子激活均参与了DFU和CLE的发生发展。蛋白质-蛋白质相互作用网络（PPI）和子模块分析确定了7个共同关键基因（分别是 、 、 、 、 、 、 ）的富集。基于这7个关键基因，我们进一步鉴定出5种微小RNA（has-mir-532-5p、has-mir-324-3p、has-mir-106a-5p、has-mir-20a-5p、has-mir-93-5p）和7种转录因子，包括CEBPA、CEBPB、GLI1、EP30D、JUN、SP1、NFE2L2作为潜在的上游分子。功能性免疫浸润分析表明这些基因与免疫细胞有关。使用CIBERSORT算法和皮尔逊方法确定关键基因与免疫细胞之间的相关性，发现DFU和CLE之间存在相反的关键基因-免疫细胞相关性。最后，DGIbd数据库表明帕喹莫德和他喹莫德可用于靶向S100A9，利巴韦林可用于靶向OASL。我们的研究结果突出了DFU和CLE之间共同的基因表达特征和信号通路，表明这两种疾病之间存在密切关联。这为靶向治疗的开发和相互作用提供了指导。
