EGCG identified as an autophagy inducer for rosacea therapy

Background: Rosacea is a common facial skin inflammatory disease featured by hyperactivation of mTORC1 signaling in the epidermis. Due to unclear pathogenesis, the effective treatment options for rosacea remain limited.Methods: Weighted gene co-expression network analysis (WGCNA) analyzed the relati...

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Main Authors: Lei Zhou, Yun Zhong, Yaling Wang, Zhili Deng, Yingxue Huang, Qian Wang, Hongfu Xie, Yiya Zhang, Ji Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2023.1092473/full
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author Lei Zhou
Lei Zhou
Yun Zhong
Yun Zhong
Yaling Wang
Yaling Wang
Zhili Deng
Zhili Deng
Zhili Deng
Yingxue Huang
Yingxue Huang
Qian Wang
Hongfu Xie
Hongfu Xie
Hongfu Xie
Yiya Zhang
Yiya Zhang
Yiya Zhang
Ji Li
Ji Li
Ji Li
author_facet Lei Zhou
Lei Zhou
Yun Zhong
Yun Zhong
Yaling Wang
Yaling Wang
Zhili Deng
Zhili Deng
Zhili Deng
Yingxue Huang
Yingxue Huang
Qian Wang
Hongfu Xie
Hongfu Xie
Hongfu Xie
Yiya Zhang
Yiya Zhang
Yiya Zhang
Ji Li
Ji Li
Ji Li
author_sort Lei Zhou
collection DOAJ
description Background: Rosacea is a common facial skin inflammatory disease featured by hyperactivation of mTORC1 signaling in the epidermis. Due to unclear pathogenesis, the effective treatment options for rosacea remain limited.Methods: Weighted gene co-expression network analysis (WGCNA) analyzed the relationship between epidermis autophagy and mTOR pathways in rosacea, and further demonstrated it through immunofluorescence and qPCR analysis. A potential therapeutic agent for rosacea was predicted based on the key genes of the WGCNA module. In vivo and in vitro experiments were conducted to verify its therapeutic role. Drug–target prediction (TargetNet, Swiss, and Tcmsp) and molecular docking offered potential pharmacological targets.Results: WGCNA showed that epidermis autophagy was related to the activation of mTOR pathways in rosacea. Next, autophagy was downregulated in the epidermis of rosacea, which was regulated by mTOR. In addition, the in vivo experiment demonstrated that autophagy induction could be an effective treatment strategy for rosacea. Subsequently, based on the key genes of the WGCNA module, epigallocatechin-3-gallate (EGCG) was predicted as a potential therapeutic agent for rosacea. Furthermore, the therapeutic role of EGCG on rosacea was confirmed in vivo and in vitro. Finally, drug–target prediction and molecular docking revealed that AKT1/MAPK1/MMP9 could be the pharmacological targets of EGCG in rosacea.Conclusion: Collectively, our findings revealed the vital role of autophagy in rosacea and identified that EGCG, as a therapeutic agent for rosacea, attenuated rosacea-like inflammation via inducing autophagy in keratinocytes.
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spelling doaj.art-ec9dcc44094f4004aa490adb93393f202023-03-01T04:48:25ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-03-011410.3389/fphar.2023.10924731092473EGCG identified as an autophagy inducer for rosacea therapyLei Zhou0Lei Zhou1Yun Zhong2Yun Zhong3Yaling Wang4Yaling Wang5Zhili Deng6Zhili Deng7Zhili Deng8Yingxue Huang9Yingxue Huang10Qian Wang11Hongfu Xie12Hongfu Xie13Hongfu Xie14Yiya Zhang15Yiya Zhang16Yiya Zhang17Ji Li18Ji Li19Ji Li20Department of Dermatology, Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Dermatology, Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Dermatology, Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Dermatology, Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Dermatology, Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, ChinaHunan Binsis Biotechnology Co, Ltd., Changsha, ChinaDepartment of Dermatology, Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Dermatology, Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Dermatology, Xiangya Hospital, Central South University, Changsha, ChinaHunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaBackground: Rosacea is a common facial skin inflammatory disease featured by hyperactivation of mTORC1 signaling in the epidermis. Due to unclear pathogenesis, the effective treatment options for rosacea remain limited.Methods: Weighted gene co-expression network analysis (WGCNA) analyzed the relationship between epidermis autophagy and mTOR pathways in rosacea, and further demonstrated it through immunofluorescence and qPCR analysis. A potential therapeutic agent for rosacea was predicted based on the key genes of the WGCNA module. In vivo and in vitro experiments were conducted to verify its therapeutic role. Drug–target prediction (TargetNet, Swiss, and Tcmsp) and molecular docking offered potential pharmacological targets.Results: WGCNA showed that epidermis autophagy was related to the activation of mTOR pathways in rosacea. Next, autophagy was downregulated in the epidermis of rosacea, which was regulated by mTOR. In addition, the in vivo experiment demonstrated that autophagy induction could be an effective treatment strategy for rosacea. Subsequently, based on the key genes of the WGCNA module, epigallocatechin-3-gallate (EGCG) was predicted as a potential therapeutic agent for rosacea. Furthermore, the therapeutic role of EGCG on rosacea was confirmed in vivo and in vitro. Finally, drug–target prediction and molecular docking revealed that AKT1/MAPK1/MMP9 could be the pharmacological targets of EGCG in rosacea.Conclusion: Collectively, our findings revealed the vital role of autophagy in rosacea and identified that EGCG, as a therapeutic agent for rosacea, attenuated rosacea-like inflammation via inducing autophagy in keratinocytes.https://www.frontiersin.org/articles/10.3389/fphar.2023.1092473/fullrosaceaEGCGmTORautophagyskin inflammation
spellingShingle Lei Zhou
Lei Zhou
Yun Zhong
Yun Zhong
Yaling Wang
Yaling Wang
Zhili Deng
Zhili Deng
Zhili Deng
Yingxue Huang
Yingxue Huang
Qian Wang
Hongfu Xie
Hongfu Xie
Hongfu Xie
Yiya Zhang
Yiya Zhang
Yiya Zhang
Ji Li
Ji Li
Ji Li
EGCG identified as an autophagy inducer for rosacea therapy
Frontiers in Pharmacology
rosacea
EGCG
mTOR
autophagy
skin inflammation
title EGCG identified as an autophagy inducer for rosacea therapy
title_full EGCG identified as an autophagy inducer for rosacea therapy
title_fullStr EGCG identified as an autophagy inducer for rosacea therapy
title_full_unstemmed EGCG identified as an autophagy inducer for rosacea therapy
title_short EGCG identified as an autophagy inducer for rosacea therapy
title_sort egcg identified as an autophagy inducer for rosacea therapy
topic rosacea
EGCG
mTOR
autophagy
skin inflammation
url https://www.frontiersin.org/articles/10.3389/fphar.2023.1092473/full
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