MicroRNA expression signature and the therapeutic effect of the microRNA-21 antagomir in hypertrophic scarring

Abstract

Hypertrophic scars (HS) area fibroproliferative disorder of the skin, which causes aesthetic and functional impairment. However, the molecular pathogenesis of this disease remains largely unknown and currently no efficient treatment exists. MicroRNAs (miRNAs) are involved in a variety of pathophysiological processes, however the role of miRNAs in HS development remains unclear. To investigate the miRNA expression signature of HS, microarray analysis was performed and 152 miRNAs were observed to be differentially expressed in HS tissue compared with normal skin tissues. Of the miRNAs identified, miRNA-21 (miR-21) was significantly increased in HS tissues and hypertrophic scar fibroblasts (HSFBs) as determined by reverse transcription-quantitative polymerase chain reaction analysis. It was also observed that, when miR-21 in HSFBs was blocked through use of an antagomir, the phenotype of fibrotic fibroblasts in vitro was reversed, as demonstrated by growth inhibition, induction of apoptosis and suppressed expression of fibrosis-associated genes collagen type I α 1 chain (COL1A1), COL1A2 and fibronectin. Furthermore, miR-21 antagomir administration significantly reduced the severity of HS formation and decreased collagen deposition in a rabbit ear HS model. The total scar area and scar elevation index were calculated and were demonstrated to be significantly decreased in the treatment group compared with control rabbits. These results indicated that the miR-21 antagomir has a therapeutic effect on HS and suggests that targeting miRNAs may be a successful and novel therapeutic strategy in the treatment of fibrotic diseases that are difficult to treat with existing methods.

Molecular mechanism of myofibroblast formation and strategies for clinical drugs treatments in hypertrophic scars

“…Microarray analysis revealed that at least 152 miRNAs were altered in the expression of HTS, including 82 upregulated miRNAs and 70 downregulated miRNAs. High expression of miRNA downregulated the core proteoglycan expression to promote hyperplasia of fibrous scar tissue (Guo et al, ). It was reported miR‐21 was upregulated, and the expression level was 5.5l times higher than that in normal skin tissue.…”

miR-495 inhibits the growth of fibroblasts in hypertrophic scars

“…The tissue under the experimental wounds were injected with 100 µl of solution containing 10 nM miR-495 agomir (one side) or control (the other side). The injections were carried out on days 5 and 10 after wounding [30]. After recording was the initial area of the wound, the size of the wound was recorded regularly, as was the time required for wound healing.…”

Advances in scarless foetal wound healing and prospects for scar reduction in adults

“…Interestingly, miRNAs are characterized by dynamic changes during embryonic development and usually suppress expression of factors in foetal wounds 99 . In Table 2, we present a summary of research primarily focused on the impact of miRNAs in scar formation during the adult stage 100‐120 . Differentially expressed miRNAs have been detected between scar lesions in adult versus embryonic skin 36,121 .…”