Genetic Risk Factor for Diabetic Foot Complications

NewsBot · Aug 1, 2024

Comprehensive transcriptomic analysis of immune-related genes in diabetic foot ulcers: New insights into mechanisms and therapeutic targets
Nan Jiang et al
Int Immunopharmacol. 2024 Jul 29:139:112638.

Background: Diabetic foot ulcers (DFU), affecting a quarter of diabetic patients and leading to high rates of amputation and mortality, pose significant health and economic burdens. Wound healing in DFU is often compromised by chronic inflammation, underscoring the critical role of immune cells. However, the systematic investigation of immune-related genes (IRGs) in DFU pathogenesis remains elusive. To address this gap, our study aims to explore the association between IRGs and DFU.

Methods: To explore biological changes in immune related gene expression in DFU, RNA-seq was performed on wound biopsies derived from 10 DFU patients and 11 healthy controls. Differentially expressed genes (DEGs) between DFU and normal samples were obtained by DEseq2. By intersecting the IRG list from the ImmPort database, the immune-related differentially expressed genes were identified. Function enrichment analysis and protein-protein interaction (PPI) analysis were applied by clusterProfiler and STRING database, and the hub genes of the PPI network were calculated by the cytoHubba plug-ins in Cytoscape. CIBERSORT algorithms was applied to analyze immune infiltration in DFU. And the correlation between immune cells infiltration and hub genes was explored by correlation analysis. Finally, to validate our findings, the transcriptional change of hub genes in DFU was confirmed using external scRNA-seq dataset and RT-qPCR.

Results: RNA-seq analysis detected 8,800 DEGs in DFUs, with 2,351 upregulated and 6,449 downregulated.526 differential IRGs were obtained from intersection of DEGs and IRGs. 526 differential IRGs were obtained from intersection of DEGs and IRGs. Enrichment function analysis of DEGs showed that they played a significant role in immune response. The PPI network was constructed, and the most significant module containing 4 hub genes was identified. CIBERSORT analysis showing that there was a significant difference between DFU and normal controls in the infiltration of immune cells. Compared with normal tissue, DFU tissue contained a higher proportion of resting NK cell, M0 macrophages, and activated mast cell, while resting dendritic cell, activated mast cell, and activated NK cell contributed to a relatively lower portion. Additionally, the analysis for M1/M2 polarization of macrophage cells shown that DFU tissue contained a higher M1/M2 ratio than normal group. Finally, the expression levels of 4 hub genes were confirmed by external scRNA-seq dataset and RT-qPCR.

Conclusions: The immune related hub genes and the difference in immune infiltration between DFU tissue and normal controls might provide new insight for understanding DFU healing.
Click to expand...

NewsBot · Aug 15, 2024

Identification of CGNL1 as a diagnostic marker in fibroblasts of diabetic foot ulcers: Insights from single cell RNA sequencing and bulk sequencing data
Li Wang et al
Int J Immunopathol Pharmacol. 2024 Jan-Dec:38:3946320241265945.

Objectives: This study aimed to explore the unique transcriptional feature of fibroblasts subtypes and the role of ferroptosis in diabetic foot ulcers (DFUs).

Methods: The GEO (Gene Expression Omnibus) was searched to obtain the DFUs single-cell and transcriptional datasets. After identifying cell types by classic marker genes, the integrated single-cell dataset was used to run trajectory inference, RNA velocity, and ligand-receptor interaction analysis. Next, bulk RNA-seq datasets of DFUs were analyzed to the key ferroptosis genes.

Results: Here, we profile 83529 single transcriptomes from the foot samples utilizing single-cell sequencing (scRNA-seq) data of DFU from GEO database and identified 12 cell types, with fibroblasts exhibiting elevated levels of ferroptosis activity and substantial cellular heterogeneity. Our results defined six main fibroblast subsets that showed mesenchymal, secretory-reticular, secretory-papillary, pro-inflammatory, myogenesis, and healing-enriched functional annotations. Trajectory inference and cell-cell communication analysis revealed two major cell fates with subpopulations of fibroblasts and altered ligand-receptor interactions. Bulk RNA sequencing data identified CGNL1 as a distinctive diagnostic signature in fibroblasts. Notably, CGNL1 positively correlated with pro-inflammatory fibroblasts.

Conclusions: Overall, our analysis delineated the heterogeneity present in cell populations of DFUs, showing distinct fibroblast subtypes characterized by their own unique transcriptional features and enrichment functions. Our study will help us better understand DFUs pathogenesis and identifies CGNL1 as a potential target for DFUs therapies.
Click to expand...

NewsBot · Sep 24, 2024

Identification and clinical validation of the role of anoikis‐related genes in diabetic foot
Nan Su, et al
Int Wound J. 2024 Mar; 21(3): e14771.

This study aims to investigate the role of anoikis‐related genes in diabetic foot (DF) by utilizing bioinformatics analysis to identify key genes associated with anoikis in DF. We selected the GEO datasets GSE7014, GSE80178 and GSE68183 for the extraction and analysis of differentially expressed anoikis‐related genes (DE‐ARGs). GO analysis and KEGG analysis indicated that DE‐ARGs in DF were primarily enriched in apoptosis, positive regulation of MAPK cascade, anoikis, focal adhesion and the PI3K‐Akt signalling pathway. Based on the LASSO and SVM‐RFE algorithms, we identified six characteristic genes. ROC curve analysis revealed that these six characteristic genes had an area under the curve (AUC) greater than 0.7, indicating good diagnostic efficacy. Expression analysis in the validation set revealed downregulation of CALR in DF, consistent with the training set results. GSEA results demonstrated that CALR was mainly enriched in blood vessel morphogenesis, endothelial cell migration, ECM‐receptor interaction and focal adhesion. The HPA database revealed that CALR was moderately enriched in endothelial cells, and CALR was found to interact with 63 protein‐coding genes. Functional analysis with DAVID suggested that CALR and associated genes were enriched in the phagosome component. CALR shows promise as a potential marker for the development and treatment of DF.
Click to expand...

Genetic Risk Factor for Diabetic Foot Complications

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

Genetic risk factors for plantar fasciitis

Genetic risk factors for an ankle sprain

Genetic risk factors for posterior tibial tendon dysfunction

Genetic Risk Factors for Musculoskeletal Soft Tissue Injuries.

A Possible Alternative to Proprioceptive Insoles – Epigenetics

Abnormal Ontogenetic Development of the Calcaneus resulting in the PreClinical Clubfoot Deformity

phylogenetics query

Share This Page

Genetic Risk Factor for Diabetic Foot Complications

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

NewsBot The Admin that posts the news.

Genetic risk factors for plantar fasciitis

Genetic risk factors for an ankle sprain

Genetic risk factors for posterior tibial tendon dysfunction

Genetic Risk Factors for Musculoskeletal Soft Tissue Injuries.

A Possible Alternative to Proprioceptive Insoles – Epigenetics

Abnormal Ontogenetic Development of the Calcaneus resulting in the PreClinical Clubfoot Deformity

phylogenetics query

Share This Page

Useful Searches