Comparative Genomic, MicroRNA, and Tissue Analyses Reveal Subtle Differences between Non-Diabetic and Diabetic Foot Skin
| Autor: | Horacio Ramirez, Robert S. Kirsner, Anna G. Maione, Marjana Tomic-Canic, Olivera Stojadinovic, Thomas G. Zwick, Irena Pastar, Liang Liang, Jonathan A. Garlick, Ashley M. Rosa |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Pathology Transcription Genetic lcsh:Medicine Biology Dermis Diabetes mellitus microRNA Gene expression medicine Humans lcsh:Science Foot Ulcer Multidisciplinary Gene Expression Profiling lcsh:R Histology Genomics Fibroblasts medicine.disease Diabetic foot Diabetic Foot 3. Good health Surgery Gene expression profiling MicroRNAs medicine.anatomical_structure lcsh:Q Epidermis Wound healing Research Article |
| Zdroj: | PLoS ONE, Vol 10, Iss 8, p e0137133 (2015) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | Diabetes Mellitus (DM) is a chronic, severe disease rapidly increasing in incidence and prevalence and is associated with numerous complications. Patients with DM are at high risk of developing diabetic foot ulcers (DFU) that often lead to lower limb amputations, long term disability, and a shortened lifespan. Despite this, the effects of DM on human foot skin biology are largely unknown. Thus, the focus of this study was to determine whether DM changes foot skin biology predisposing it for healing impairment and development of DFU. Foot skin samples were collected from 20 patients receiving corrective foot surgery and, using a combination of multiple molecular and cellular approaches, we performed comparative analyses of non-ulcerated non-neuropathic diabetic foot skin (DFS) and healthy non-diabetic foot skin (NFS). MicroRNA (miR) profiling of laser captured epidermis and primary dermal fibroblasts from both DFS and NFS samples identified 5 miRs de-regulated in the epidermis of DFS though none reached statistical significance. MiR-31-5p and miR-31-3p were most profoundly induced. Although none were significantly regulated in diabetic fibroblasts, miR-29c-3p showed a trend of up-regulation, which was confirmed by qPCR in a prospective set of 20 skin samples. Gene expression profiling of full thickness biopsies identified 36 de-regulated genes in DFS (>2 fold-change, unadjusted p-value ≤ 0.05). Of this group, three out of seven tested genes were confirmed by qPCR: SERPINB3 was up-regulated whereas OR2A4 and LGR5 were down-regulated in DFS. However no morphological differences in histology, collagen deposition, and number of blood vessels or lymphocytes were found. No difference in proliferative capacity was observed by quantification of Ki67 positive cells in epidermis. These findings suggest DM causes only subtle changes to foot skin. Since morphology, mRNA and miR levels were not affected in a major way, additional factors, such as neuropathy, vascular complications, or duration of DM, may further compromise tissue’s healing ability leading to development of DFUs. |
| Databáze: | OpenAIRE |
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