TY - JOUR T1 - Transcriptomic Analysis of a Diabetic Skin-Humanized Mouse Model Dissects Molecular Pathways Underlying the Delayed Wound Healing Response. JF - Genes (Basel) Y1 - 2020 A1 - León, Carlos A1 - Garcia-Garcia, Francisco A1 - Llames, Sara A1 - García-Pérez, Eva A1 - Carretero, Marta A1 - Arriba, María Del Carmen A1 - Dopazo, Joaquin A1 - Del Rio, Marcela A1 - Escamez, Maria José A1 - Martínez-Santamaría, Lucía KW - Animals KW - Diabetes Mellitus, Experimental KW - Gene Expression Profiling KW - Gene Expression Regulation KW - Gene ontology KW - Humans KW - Metabolic Networks and Pathways KW - Mice KW - Mice, Nude KW - Microarray Analysis KW - Molecular Sequence Annotation KW - Principal Component Analysis KW - Signal Transduction KW - Skin KW - Skin Transplantation KW - Skin Ulcer KW - Streptozocin KW - Tissue Engineering KW - Transcriptome KW - Transplantation, Heterologous KW - Wound Healing AB -

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.

VL - 12 IS - 1 U1 - https://www.ncbi.nlm.nih.gov/pubmed/33396192?dopt=Abstract ER -