miRNAs as Regulators of the Early Local Response to Burn Injuries

Abstract

In burn injuries, risk factors and limitations to treatment success are difficult to assess clinically. However, local cellular responses are characterized by specific gene-expression patterns. MicroRNAs (miRNAs) are single-stranded, non-coding RNAs that regulate mRNA expression on a posttranscriptional level. Secreted through exosome-like vesicles (ELV), miRNAs are intracellular signalers and epigenetic regulators. To date, their role in the regulation of the early burn response remains unclear. Here, we identified 43 miRNAs as potential regulators of the early burn response through the bioinformatics analysis of an existing dataset. We used an established human ex vivo skin model of a deep partial-thickness burn to characterize ELVs and miRNAs in dermal interstitial fluid (dISF). Moreover, we identified miR-497-5p as stably downregulated in tissue and dISF in the early phase after a burn injury. MiR-218-5p and miR-212-3p were downregulated in dISF, but not in tissue. Target genes of the miRNAs were mainly upregulated in tissue post-burn. The altered levels of miRNAs in dISF of thermally injured skin mark them as new biomarker candidates for burn injuries. To our knowledge, this is the first study to report miRNAs altered in the dISF in the early phase of deep partial-thickness burns.

Burn-injured skin is marked by a prolonged local acute inflammatory response of innate immune cells and pro-inflammatory cytokines

“…In burn tissue from PBW 2-4, the levels of IL-1α, IL-18 and IL-33 were returning to the levels in healthy skin, which may be related to the presence of keratinocytes closing the defect. Levels of cytokines, as well as microRNAs ( 35 ), could be potential biomarkers to predict disease progression or recovery ( 36 ).…”

MicroRNAs involved in human skin burns, wound healing and scarring

“…[15][16][17] This review will only include previous human research. Samples used to study burn-related miRNAs include adult skin fibroblasts, [18][19][20][21] skin epidermal stem cells, 22 skin, [23][24][25][26][27] wound tissues 28,29 and hypertrophic scar (HS) tissues. [30][31][32][33] Samples used to study wound-healing related miRNAs include healthy skin, [34][35][36] chronic non-healing ulcer tissue, 37,38 epidermal keratinocytes 39 and the HaCaT cell line.…”

“…Other techniques include microarrays (miRCURY LNA, Affymetrix GeneChip, and Agilent) and high throughput sequencing. Although qRT-PCR is the most commonly used technique, only 58 miRNAs were identified in the 27 articles that utilised the technique, [18][19][20][21][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][45][46][47][48][49][50] while the expression level of 82 miRNAs were measured by sequencing in two research studies. 22,38 In comparison, alterations in the expression of 203 miRNAs were detected using three different microarrays in seven research studies.…”

Extracellular Vesicles as Regulators of Immune Function in Traumatic Injuries and Sepsis

“…miR-497, an miRNA upregulated in hypertrophic scars, was persistently downregulated after burn. The degree of loss of miR-497 could be used an indicator for the regenerative capacity of an individual’s injured tissue a burn injury ( 73 ). This becomes important, because there is currently no diagnostic metric to help burn surgeons decide when to surgically restore wounds after burn injury.…”