%0 Journal Article
%T CircRNA-406918 enhances the degradation of advanced glycation end products in photoaged human dermal fibroblasts via targeting cathepsin D.
%A Qu Y
%A Wang M
%A Lan J
%A Huang X
%A Huang J
%A Li H
%A Zheng Y
%A Xu Q
%J Photodermatol Photoimmunol Photomed
%V 39
%N 5
%D 2023 Sep 30
%M 37253092
%F 3.254
%R 10.1111/phpp.12887
%X <B>BACKGROUND: </B>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.<BR><B>OBJECTIVE: </B>To explore possible mechanism of regulating CTSD expression in photoaged fibroblasts.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.