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| Status |
Public on Aug 01, 2020 |
| Title |
RNA-sequencing analysis of forearm skin in diabetic patients with or without foot ulcerations |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Diabetic foot ulcers (DFUs) and associated impaired healing, represent a major problem, that significantly impairs the quality of life of diabetic patients, leading to prolonged hospitalization and resulting in more than 70,000 lower extremity amputations per year in the USA alone. In the present study, we prospectively followed a large group of DFU patients for 12 weeks and aimed to identify systemic and local factors that are associated with DFU healing. We also studied healthy control subjects and diabetic patients without DFU and compared differences with the DFU patients. We first employed serum multiplex arrays to detect systemic cytokines, chemokines and growth factors, which correlate with DFU healing. In addition, we collected forearm biopsies for histology and bulk transcriptome analyses to establish whether DFU healing outcome was reflected at a non-ulcerative skin site. Bulk RNA-seq analysis revealed extracellular matrix (ECM) related genes up-regulated in Healers, including MMP2 as well as implication of IFNγ and IL13 as upstream regulators. According to transcriptome data analysis with a false discovery rate (FDR) <0.05 and log2 fold-change (log2FC) > 0.5, a total of 25 genes (3 up-regulated) were differentially expressed when comparing Non-Healers and Healers, 916 (530 up-regulated) in Healers compared to DM and 160 (89 up-regulated) in Non-Healers compared to DM. Genes of interest that were increased in Healers include inflammation associated molecules lymphoid chemokine ligand 19 (CCL19), complement component 6 (C6), lipoprotein lipase (LPL) and beta-defensin 124 (DEFB124), as well as extracellular matrix linked proteins pigment-epithelium derived factor (SERPINF1), tenascin X (TNXB), biglycan (BGN) and matrix metalloproteinase-2 (MMP2). For Non-Healers, up-regulated genes were cytochrome P450 family member (CYP1A1), prostaglandin transporter (SLCO2A1) and metabolism regulator G0/G1 switch gene 2 (G0S2).
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| Overall design |
mRNA profiles from skin isolated from the volar aspect of the forearm from 13 diabetic patients; 5 who healed their ulcers, 4 who didn't heal and 4 who had no ulcers.
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| Contributor(s) |
Theocharidis G, Patsopoulos N |
| Citation(s) |
32763913 |
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| Submission date |
Jan 15, 2020 |
| Last update date |
Aug 13, 2020 |
| Contact name |
Aristidis Veves |
| E-mail(s) |
aveves@bidmc.harvard.edu
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| Phone |
6176627075
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| Organization name |
Beth Israel Deaconess Medical Center
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| Lab |
Rongxiang Xu, MD, Center for Regenerative Therapeutics
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| Street address |
330 Brookline Ave
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (13)
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| GSM4273448 |
forearm, no ulcer, X204_s |
| GSM4273449 |
forearm, ulcer healer, X206_s |
| GSM4273450 |
forearm, ulcer healer, X207_s |
| GSM4273451 |
forearm, ulcer healer, X208_s |
| GSM4273452 |
forearm, ulcer healer, X209_s |
| GSM4273453 |
forearm, ulcer healer, X210_s |
| GSM4273454 |
forearm, ulcer nonhealer, X211_s |
| GSM4273455 |
forearm, ulcer nonhealer, X212_s |
| GSM4273456 |
forearm, ulcer nonhealer, X213_s |
| GSM4273457 |
forearm, ulcer nonhealer, X215_s |
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| Relations |
| BioProject |
PRJNA601464 |
| SRA |
SRP242087 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE143735_RAW.tar |
12.0 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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