Resveratrol inhibits hypertrophic scars formation by activating autophagy via the miR-4654/Rheb axis

Hypertrophic scars (HSs) are a type of pathological scar which are induced by surgery, burn injuries or trauma during the healing process. Due to the high recurrence rates and strong invasive properties, HSs have become a major clinical issue. Resveratrol has been identified as a potential agent to...

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Veröffentlicht in:Molecular medicine reports 2020-10, Vol.22 (4), p.3440-3452
Hauptverfasser: Pang, Kun, Li, Bibo, Tang, Zhiming, Yang, Wen, Hao, Lin, Shi, Zhenduo, Zhang, Jianjun, Cai, Longjun, Li, Rui, Liu, Ying, Lv, Qian, Ding, Jicun, Han, Conghui
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Sprache:eng
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Zusammenfassung:Hypertrophic scars (HSs) are a type of pathological scar which are induced by surgery, burn injuries or trauma during the healing process. Due to the high recurrence rates and strong invasive properties, HSs have become a major clinical issue. Resveratrol has been identified as a potential agent to suppress scar formation; however, the underlying mechanism of action remains unclear. Therefore, the present study aimed to investigate the effect of resveratrol on HS-derived fibroblasts (HSFBs) in vitro. MTT assay was performed to evaluate cell viability following the resveratrol treatment. Western blot and RT-qPCR analysis was used to identify the expression levels and the relationship among autophagic markers, miR-4654 and resveratrol treatment. Finally, GFP-LC3 stable HSFBs cells were generated to further assess the effect of resveratrol. The results revealed that resveratrol significantly induced cell death in a dose-dependent manner and induced autophagy by downregulating the expression levels of Rheb in HSFBs. Notably, microRNA-4654 (miR-4654) was significantly decreased in the HSFBs and re-upregulated by resveratrol treatment dose-dependently. Through the bioinformatic analysis and luciferase assay, miR-4654 was identified to directly target Rheb. Transfection studies showed that miR-4654 negative correlated with Rheb expression, suggesting that the autophagic process may be altered by the miR-4654/Rheb axis under the control of resveratrol. In conclusion, the results of the present study suggested that resveratrol may promote autophagy by upregulating miR-4654, which in turn may suppress Rheb expression via directly binding to the 3'-untranslated region of Rheb. These findings provided a novel insight into the development of potential therapeutic targets for HSs.
ISSN:1791-2997
1791-3004
DOI:10.3892/mmr.2020.11407