Transcriptomic Analysis of a Diabetic Skin-Humanized Mouse Model Dissects Molecular Pathways Underlying the Delayed Wound Healing Response.

TitleTranscriptomic Analysis of a Diabetic Skin-Humanized Mouse Model Dissects Molecular Pathways Underlying the Delayed Wound Healing Response.
Publication TypeJournal Article
Year of Publication2020
AuthorsLeón, C, Garcia-Garcia, F, Llames, S, García-Pérez, E, Carretero, M, Arriba, MDel Carmen, Dopazo, J, Del Rio, M, Escamez, MJosé, Martínez-Santamaría, L
JournalGenes (Basel)
Date Published2020 12 31
KeywordsAnimals; Diabetes Mellitus, Experimental; Gene Expression Profiling; Gene Expression Regulation; Gene ontology; Humans; Metabolic Networks and Pathways; Mice; Mice, Nude; Microarray Analysis; Molecular Sequence Annotation; Principal Component Analysis; Signal Transduction; Skin; Skin Transplantation; Skin Ulcer; Streptozocin; Tissue Engineering; Transcriptome; Transplantation, Heterologous; Wound Healing

Defective healing leading to cutaneous ulcer formation is one of the most feared complications of diabetes due to its consequences on patients' quality of life and on the healthcare system. A more in-depth analysis of the underlying molecular pathophysiology is required to develop effective healing-promoting therapies for those patients. Major architectural and functional differences with human epidermis limit extrapolation of results coming from rodents and other small mammal-healing models. Therefore, the search for reliable humanized models has become mandatory. Previously, we developed a diabetes-induced delayed humanized wound healing model that faithfully recapitulated the major histological features of such skin repair-deficient condition. Herein, we present the results of a transcriptomic and functional enrichment analysis followed by a mechanistic analysis performed in such humanized wound healing model. The deregulation of genes implicated in functions such as angiogenesis, apoptosis, and inflammatory signaling processes were evidenced, confirming published data in diabetic patients that in fact might also underlie some of the histological features previously reported in the delayed skin-humanized healing model. Altogether, these molecular findings support the utility of such preclinical model as a valuable tool to gain insight into the molecular basis of the delayed diabetic healing with potential impact in the translational medicine field.

Alternate JournalGenes (Basel)
PubMed ID33396192
PubMed Central IDPMC7824036
Grant ListSAF2017-86810-R / / Spanish Ministry of Economy and Competitiveness /
SAF2010-16976 / / Spanish Ministry of Economy and Competitiveness /
ISCIII PT17/0009/0015 FEDER / / FEDER /