Hypertrophic scar (HS) is a fibrotic disease in which excessive extracellular matrix forms due to the response of fibroblasts to tissue damage. Novel evidence suggests that microRNAs (miRNAs or miRs) may contribute to hypertrophic scarring; however, the role of miRNAs in HS formation remains unclear. In the present study, miR-26a was significantly downregulated in HS tissues and human HS fibroblasts (hHSFs) was detected by reverse transcription-quantitative analysis. TargetScan was used to predict that mothers against decapentaplegic homolog 2 (Smad2) is a potential target gene of miR-26a and a dual-luciferase reporter assay confirmed that Smad2 was a target gene of miR-26a. The expression of Smad2 was upregulated in HS tissues and hHSFs. Cell Counting Kit-8 and flow cytometry analyses demonstrated that the overexpression of miR-26a significantly suppressed the proliferation ability of hHSFs and the apoptotic rate of hHSFs was significantly upregulated in response to miR-26a mimic transfection. Furthermore, the expression of B-cell lymphoma-2 (Bcl-2)-associated X protein was increased and Bcl-2 expression was decreased following miR-26a mimic transfection. The expression of collagens I and III was significantly inhibited following treatment with miR-26a mimics in hHSF cells. Conversely, miR-26a inhibitors served an opposing role in hHSFs. Furthermore, Smad2 overexpression enhanced the expression of collagens I and c III; however, Smad2 silencing inhibited the expression of collagens I and c III. In conclusion, the results of the present study indicate that miR-26a inhibits HS formation by modulating proliferation and apoptosis ad well as inhibiting the expression of extracellular matrix-associated proteins by targeting Smad2.
Hypertrophic scar (HS) formation is the result of poor skin-wound healing. At present, the pathogenesis of HS formation is largely unclear. Micro (miR)RNAs have important effects on a variety of biological and pathological processes. The role of miRNA in HS formation remains largely unclear. The present study aimed to investigate the role of miR-205-5p in HS, and explore the underlying molecular mechanism. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression of miR-205-5p in HS. Western blot assay and RT-qPCR were performed to assess the expression of associated proteins and genes, respectively. TargetScan was performed to predict the target gene of miR-205-5p, and the luciferase reporter assay was applied to verify the prediction. The function of miR-205-5p on cell proliferation was detected using Cell Counting Kit-8 assay, and cell apoptosis was detected via flow cytometry. miR-205-5p expression was decreased in HS tissues and human hypertrophic scar fibroblasts (hHSFs). Mothers against decapentaplegic homolog (Smad)2 was significantly increased in HS tissues and HSFs, and it was directly targeted by miR-205-5p. Restoration of miR-205-5p suppressed HSF cell proliferation and induced cell apoptosis. It was also demonstrated that RAC-Alpha Serine/Threonine-Protein Kinase (AKT) phosphorylation and the expression of α-smooth muscle actin, collagen I and collagen III were inhibited by miR-205-5p. In addition, Smad2 weakened the effects of miR-205-5p on HSFs. In conclusion, miR-205-5p exhibited an important role in HS by targeting smad2 and suppressing the AKT pathway. These findings provide a clearer understanding of the mechanism for HS that may be used to develop novel treatments for HS.
Burns can impair the barrier function of the skin, and small burns can also cause high mortality. The WHO has described that over 180,000 people die of burns worldwide each year. Thus, the treatment of burn wounds is a major clinical challenge. Chitooligosaccharides (COS) are alkaline amino oligosaccharides with small molecular weights obtained by enzyme or chemical degradation of chitosan. With the characteristics of biocompatibility, water solubility and degradability, it has attracted increasing attention in the fields of biomedicine. In the present study, we used COS to treat deep second-degree burn wounds of rat skin and found that COS was able to promote wound healing. We also revealed that COS could promote fibroblast proliferation. Transcriptome sequencing analysis was performed on COS-treated fibroblasts to identify the underlying mechanisms. The results showed that COS was able to promote wound healing through regulation of the mitogen-activated protein kinase (MAPK) pathway and growth factor Hepatocyte Growth Factor (HGF). Our results provide a potential drug for burn wound therapy and the related molecular mechanism.
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