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Isolation, Expansion, and Adipogenic Induction of CD34+CD31+ Endothelial Cells from Human Omental and Subcutaneous Adipose Tissue
Published on: July 17, 2018
ANKRD46 as a shared diagnostic and therapeutic marker in keloid and type 2 diabetes mellitus identified via multi
Tingting Yu1, Fang Liu2, Yiyi Gong2
1Department of Dermatology, Pudong New Area People's Hospital, Shanghai, China.
Background:
Keloids and Type 2 diabetes mellitus (T2DM) involve chronic inflammation and impaired wound healing. Exploring their molecular similarities may reveal their shared therapeutic targets.
Methods:
We conducted a multi-omics analysis utilizing RNA expression data from keloid and T2DM samples. Differential expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA) were applied to identify shared differentially expressed genes (DEGs). Functional enrichment analysis and immune infiltration profiling were performed to elucidate the underlying biological pathways. To identify diagnostic biomarkers, machine learning techniques, including LASSO and SVM-RFE, were employed. The experimental validation of ANKRD46 was carried out using Western blotting, qRT-PCR, IHC, flow cytometry, and the establishment of mouse models.
Results:
A total of 20 DEGs were found to overlap between keloids and T2DM, with significant enrichment in pathways related to glucose metabolism and immune responses. ANKRD46 emerged as a robust diagnostic marker, demonstrating strong correlations with immune cells, including plasmacytoid dendritic cells and activated B cells. Experimental validation confirmed the upregulation of ANKRD46 in both conditions, with AUC values exceeding 0.75 in diagnostic models. Functional studies further confirmed a strong association between ANKRD46 and the IL6-JAK-STAT3 signaling pathway, with miR-21 regulating its expression within the fibrotic microenvironment.
Conclusion:
ANKRD46 is a promising shared diagnostic and therapeutic target for keloids and T2DM, with its role in regulating immune responses and fibrosis supported by both computational and experimental data. This study highlights the potential of ANKRD46 in modulating the IL6-JAK-STAT3 pathway, providing a foundation for future therapeutic strategies targeting both diseases.
Insights
Keloids and Type 2 diabetes share inflammation and healing issues. ANKRD46 is identified as a key diagnostic marker and potential therapeutic target for both conditions.
Area of Science:
- Biomedical Science
- Molecular Biology
- Genomics
Background:
- Keloids and Type 2 diabetes mellitus (T2DM) are characterized by chronic inflammation and impaired wound healing.
- Investigating molecular commonalities may uncover shared therapeutic targets for these distinct conditions.
Purpose of the Study:
- To identify shared molecular mechanisms and diagnostic biomarkers between keloids and T2DM.
- To explore ANKRD46 as a potential therapeutic target.
Main Methods:
- Multi-omics analysis of RNA expression data from keloid and T2DM samples.
- Differential gene expression analysis, Weighted Gene Co-expression Network Analysis (WGCNA), and machine learning (LASSO, SVM-RFE) were employed.
- Experimental validation included Western blotting, qRT-PCR, IHC, flow cytometry, and mouse models.
Main Results:
- Twenty differentially expressed genes (DEGs) overlapped between keloids and T2DM, enriched in glucose metabolism and immune response pathways.
- ANKRD46 was identified as a robust diagnostic marker, correlating with immune cells like plasmacytoid dendritic cells and activated B cells.
- ANKRD46 upregulation was confirmed experimentally, with diagnostic models showing AUC > 0.75. Its association with the IL6-JAK-STAT3 pathway and regulation by miR-21 was established.
Conclusions:
- ANKRD46 serves as a promising shared diagnostic and therapeutic target for keloids and T2DM.
- ANKRD46's role in immune response and fibrosis regulation, particularly via the IL6-JAK-STAT3 pathway, is supported by computational and experimental evidence.
- This study provides a basis for developing novel therapeutic strategies targeting ANKRD46 for both keloids and T2DM.

