{"title":"CircRNA-406918 enhances the degradation of advanced glycation end products in photoaged human dermal fibroblasts via targeting cathepsin D.","authors":"Yingying Qu, Mengyao Wang, Jingjing Lan, Xianyin Huang, Jingxi Huang, Hongpeng Li, Yue Zheng, Qingfang Xu","doi":"10.1111/phpp.12887","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Lysosomal cathepsin D (CTSD) can degrade internalized advanced glycation end products (AGEs) in dermal fibroblasts. CTSD expression is decreased in photoaged fibroblasts, which contributes to intracellular AGEs deposition and further plays a role in AGEs accumulation of photoaged skin. The mechanism under downregulated CTSD expression is unclear.</p><p><strong>Objective: </strong>To explore possible mechanism of regulating CTSD expression in photoaged fibroblasts.</p><p><strong>Methods: </strong>Dermal fibroblasts were induced into photoaging with repetitive ultraviolet A (UVA) irradiation. The competing endogenous RNA (ceRNA) networks were constructed to predict candidate circRNAs or miRNAs related with CTSD expression. AGEs-BSA degradation by fibroblasts was studied with flow cytometry, ELISA, and confocal microscopy. Effects of overexpressing circRNA-406918 via lentiviral transduction on CTSD expression, autophagy, AGE-BSA degradation were analyzed in photoaged fibroblasts. The correlation between circRNA-406918 and CTSD expression or AGEs accumulation in sun-exposed and sun-protected skin was studied.</p><p><strong>Results: </strong>CTSD expression, autophagy, and AGEs-BSA degradation were significantly decreased in photoaged fibroblasts. CircRNA-406918 was identified to regulate CTSD expression, autophagy, and senescence in photoaged fibroblasts. Overexpressing circRNA-406918 potently decreased senescence and increased CTSD expression, autophagic flux, and AGEs-BSA degradation in photoaged fibroblasts. Moreover, circRNA-406918 level was positively correlated with CTSD mRNA expression and negatively associated with AGEs accumulation in photodamaged skin. Further, circRNA-406918 was predicted to mediate CTSD expression through sponging eight miRNAs.</p><p><strong>Conclusion: </strong>These findings suggest that circRNA-406918 regulates CTSD expression and AGEs degradation in UVA-induced photoaged fibroblasts and might exert a role in AGEs accumulation in photoaged skin.</p>","PeriodicalId":20123,"journal":{"name":"Photodermatology, photoimmunology & photomedicine","volume":null,"pages":null},"PeriodicalIF":2.5000,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Photodermatology, photoimmunology & photomedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/phpp.12887","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/5/30 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"DERMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Lysosomal cathepsin D (CTSD) can degrade internalized advanced glycation end products (AGEs) in dermal fibroblasts. CTSD expression is decreased in photoaged fibroblasts, which contributes to intracellular AGEs deposition and further plays a role in AGEs accumulation of photoaged skin. The mechanism under downregulated CTSD expression is unclear.
Objective: To explore possible mechanism of regulating CTSD expression in photoaged fibroblasts.
Methods: Dermal fibroblasts were induced into photoaging with repetitive ultraviolet A (UVA) irradiation. The competing endogenous RNA (ceRNA) networks were constructed to predict candidate circRNAs or miRNAs related with CTSD expression. AGEs-BSA degradation by fibroblasts was studied with flow cytometry, ELISA, and confocal microscopy. Effects of overexpressing circRNA-406918 via lentiviral transduction on CTSD expression, autophagy, AGE-BSA degradation were analyzed in photoaged fibroblasts. The correlation between circRNA-406918 and CTSD expression or AGEs accumulation in sun-exposed and sun-protected skin was studied.
Results: CTSD expression, autophagy, and AGEs-BSA degradation were significantly decreased in photoaged fibroblasts. CircRNA-406918 was identified to regulate CTSD expression, autophagy, and senescence in photoaged fibroblasts. Overexpressing circRNA-406918 potently decreased senescence and increased CTSD expression, autophagic flux, and AGEs-BSA degradation in photoaged fibroblasts. Moreover, circRNA-406918 level was positively correlated with CTSD mRNA expression and negatively associated with AGEs accumulation in photodamaged skin. Further, circRNA-406918 was predicted to mediate CTSD expression through sponging eight miRNAs.
Conclusion: These findings suggest that circRNA-406918 regulates CTSD expression and AGEs degradation in UVA-induced photoaged fibroblasts and might exert a role in AGEs accumulation in photoaged skin.
期刊介绍：
The journal is a forum for new information about the direct and distant effects of electromagnetic radiation (ultraviolet, visible and infrared) mediated through skin. The divisions of the editorial board reflect areas of specific interest: aging, carcinogenesis, immunology, instrumentation and optics, lasers, photodynamic therapy, photosensitivity, pigmentation and therapy. Photodermatology, Photoimmunology & Photomedicine includes original articles, reviews, communications and editorials.
Original articles may include the investigation of experimental or pathological processes in humans or animals in vivo or the investigation of radiation effects in cells or tissues in vitro. Methodology need have no limitation; rather, it should be appropriate to the question addressed.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
