Circ_0011129 Encapsulated by the Small Extracellular Vesicles Derived from Human Stem Cells Ameliorate Skin Photoaging

Photoaging is not only the main cause of skin aging caused by exogenous factors, it is also related to a variety of skin diseases and even malignant tumors. Excessive and repeated exposure to ultraviolet radiation, especially UVA induces oxidative stress, DNA damage, inflammation, and collagen and e...

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Main Authors: Yu Zhang, Manqi Zhang, Amin Yao, Yalin Xie, Jingxiong Lin, Farooqi Sharifullah, Yixin Hong, Hongbo Chen, Fang Cheng, Wei Lai
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/23/15390
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author Yu Zhang
Manqi Zhang
Amin Yao
Yalin Xie
Jingxiong Lin
Farooqi Sharifullah
Yixin Hong
Hongbo Chen
Fang Cheng
Wei Lai
author_facet Yu Zhang
Manqi Zhang
Amin Yao
Yalin Xie
Jingxiong Lin
Farooqi Sharifullah
Yixin Hong
Hongbo Chen
Fang Cheng
Wei Lai
author_sort Yu Zhang
collection DOAJ
description Photoaging is not only the main cause of skin aging caused by exogenous factors, it is also related to a variety of skin diseases and even malignant tumors. Excessive and repeated exposure to ultraviolet radiation, especially UVA induces oxidative stress, DNA damage, inflammation, and collagen and elastin degeneration, ultimately leads to skin photoaging, manifested by skin redness, coarse wrinkles, and pigmentation even skin cancer. There has been a large demand of effective prevention and medications but approaches in the current management of photoaging are very limited. In the previous study, we found that a non-coding circular RNA circ_0011129 acts as a miR-6732-5p adsorption sponge to inhibit the reduction of type I collagen and the denaturation and accumulation of elastin in UVA-induced HDF cells photoaging model. However, in vivo instability and efficient delivery to the target cell of circRNA is a major challenge for its clinical application. Therefore, improving its stability and delivery efficiency are desired. In this study, we proposed a strategy of delivering circ_0011129 with small extracellular vesicles (sEVs) from human adipose-derived stem cells (hADSCs) to intervene in the photoaging process. The results showed that sEVs from hADSCs in 3D bioreactor culture (3D-sEVs) can prevent photoaging. Consequently, by overexpressing circ_0011129 in hADSCs, we successfully loaded it into 3D-sEVs (3D-circ-sEVs) and its protective effect was better. Our studies provide a novel approach to preventing skin photoaging, which has important clinical significance and application value for the development of non-coding RNA drugs to treat skin photoaging. We first screened out hADSCs-derived sEVs with excellent anti-oxidant effects. We then compared the sEVs collected from traditional 2D culture with 3D bioreactor culture. By miRNA-seq and GEO data analysis, we found that miRNAs in 3D-sEVs were enriched in cell activities related to apoptosis, cellular senescence, and inflammation. Subsequently, we prepared circ_0011129-loaded 3D-sEVs (3D-circ-sEVs) by overexpressing it in hADSCs for the treatment of photoaging in vitro. We proved that 3D-circ-sEVs can interfere with the process of cell photoaging and protect cells from UVA radiation damage, as well as in a H2O2-induced oxidative stress model.
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spelling doaj.art-ada94f66471d405f90c219bd5b6409b92023-11-24T11:18:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123231539010.3390/ijms232315390Circ_0011129 Encapsulated by the Small Extracellular Vesicles Derived from Human Stem Cells Ameliorate Skin PhotoagingYu Zhang0Manqi Zhang1Amin Yao2Yalin Xie3Jingxiong Lin4Farooqi Sharifullah5Yixin Hong6Hongbo Chen7Fang Cheng8Wei Lai9Department of Dermato-Venereology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, ChinaDepartment of Dermato-Venereology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, ChinaDepartment of Dermato-Venereology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, ChinaDepartment of Plastic Surgery, Sun Yat-sen University, Guangzhou 510000, ChinaDepartment of Dermato-Venereology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, ChinaSchool of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, ChinaDepartment of Dermato-Venereology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510000, ChinaPhotoaging is not only the main cause of skin aging caused by exogenous factors, it is also related to a variety of skin diseases and even malignant tumors. Excessive and repeated exposure to ultraviolet radiation, especially UVA induces oxidative stress, DNA damage, inflammation, and collagen and elastin degeneration, ultimately leads to skin photoaging, manifested by skin redness, coarse wrinkles, and pigmentation even skin cancer. There has been a large demand of effective prevention and medications but approaches in the current management of photoaging are very limited. In the previous study, we found that a non-coding circular RNA circ_0011129 acts as a miR-6732-5p adsorption sponge to inhibit the reduction of type I collagen and the denaturation and accumulation of elastin in UVA-induced HDF cells photoaging model. However, in vivo instability and efficient delivery to the target cell of circRNA is a major challenge for its clinical application. Therefore, improving its stability and delivery efficiency are desired. In this study, we proposed a strategy of delivering circ_0011129 with small extracellular vesicles (sEVs) from human adipose-derived stem cells (hADSCs) to intervene in the photoaging process. The results showed that sEVs from hADSCs in 3D bioreactor culture (3D-sEVs) can prevent photoaging. Consequently, by overexpressing circ_0011129 in hADSCs, we successfully loaded it into 3D-sEVs (3D-circ-sEVs) and its protective effect was better. Our studies provide a novel approach to preventing skin photoaging, which has important clinical significance and application value for the development of non-coding RNA drugs to treat skin photoaging. We first screened out hADSCs-derived sEVs with excellent anti-oxidant effects. We then compared the sEVs collected from traditional 2D culture with 3D bioreactor culture. By miRNA-seq and GEO data analysis, we found that miRNAs in 3D-sEVs were enriched in cell activities related to apoptosis, cellular senescence, and inflammation. Subsequently, we prepared circ_0011129-loaded 3D-sEVs (3D-circ-sEVs) by overexpressing it in hADSCs for the treatment of photoaging in vitro. We proved that 3D-circ-sEVs can interfere with the process of cell photoaging and protect cells from UVA radiation damage, as well as in a H2O2-induced oxidative stress model.https://www.mdpi.com/1422-0067/23/23/15390skin photoagingsmall extracellular vesiclescircle RNAhuman adipose-derived stem cells
spellingShingle Yu Zhang
Manqi Zhang
Amin Yao
Yalin Xie
Jingxiong Lin
Farooqi Sharifullah
Yixin Hong
Hongbo Chen
Fang Cheng
Wei Lai
Circ_0011129 Encapsulated by the Small Extracellular Vesicles Derived from Human Stem Cells Ameliorate Skin Photoaging
International Journal of Molecular Sciences
skin photoaging
small extracellular vesicles
circle RNA
human adipose-derived stem cells
title Circ_0011129 Encapsulated by the Small Extracellular Vesicles Derived from Human Stem Cells Ameliorate Skin Photoaging
title_full Circ_0011129 Encapsulated by the Small Extracellular Vesicles Derived from Human Stem Cells Ameliorate Skin Photoaging
title_fullStr Circ_0011129 Encapsulated by the Small Extracellular Vesicles Derived from Human Stem Cells Ameliorate Skin Photoaging
title_full_unstemmed Circ_0011129 Encapsulated by the Small Extracellular Vesicles Derived from Human Stem Cells Ameliorate Skin Photoaging
title_short Circ_0011129 Encapsulated by the Small Extracellular Vesicles Derived from Human Stem Cells Ameliorate Skin Photoaging
title_sort circ 0011129 encapsulated by the small extracellular vesicles derived from human stem cells ameliorate skin photoaging
topic skin photoaging
small extracellular vesicles
circle RNA
human adipose-derived stem cells
url https://www.mdpi.com/1422-0067/23/23/15390
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