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

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

doi:10.3892/mmr.2020.11407

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

Authors:
- Kun Pang
- Bibo Li
- Zhiming Tang
- Wen Yang
- Lin Hao
- Zhenduo Shi
- Jianjun Zhang
- Longjun Cai
- Rui Li
- Ying Liu
- Qian Lv
- Jicun Ding
- Conghui Han
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Affiliations: Department of Urology, Xuzhou Central Hospital, Xuzhou Clinical College Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu 221009, P.R. China, Department of Urology, Taizhou Hospital Affiliated to Nanjing University of Chinese Medicine, Taizhou, Jiangsu 225300, P.R. China, Department of Dermatology, Xuzhou Hospital Affiliated to Nanjing University of Traditional Chinese Medicine, Xuzhou, Jiangsu 221009, P.R. China , Department of Renal Disease, Shandong First Medical University, Tai'an, Shandong 271016, P.R. China , Department of Urology, Suqian People's Hospital of Nanjing Drum-Tower Hospital Group, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, Jiangsu 223800, P.R. China, Department of Burns and Plastic Surgery, Xuzhou Central Hospital, Xuzhou Clinical College Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu 221009, P.R. China
Published online on: August 4, 2020 https://doi.org/10.3892/mmr.2020.11407
Pages: 3440-3452
Copyright: © Pang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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