Shi Dongxin, Chu Haitao, Sun Yijun, He Hailun, Huang Wenyue, Pan Hua, Ma Cong, Yao Shulan, Shi Meihui, Wang Hexiao, Wu Yan
National joint Engineering Research Center for Theranostics of Immunological Skin Diseases, The First Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang, China; Department of Dermatology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
National joint Engineering Research Center for Theranostics of Immunological Skin Diseases, The First Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang, China; Department of Hyperbaric Oxygen, The First Hospital of China Medical University, Shenyang, China.
J Photochem Photobiol B. 2025 Aug;269:113188. doi: 10.1016/j.jphotobiol.2025.113188. Epub 2025 May 28.
UVA radiation can impact fibroblasts and leads to alterations in dermal connective tissue. Pyroptosis is a form of regulated cell death characterized by gasdermin-mediated membrane pore formation and release of intracellular contents. Whether UVA exposure can trigger pyroptosis in fibroblasts is unclear. Paeoniflorin has antioxidant properties, but whether it alleviates pyroptosis through inhibiting oxidative stress in fibroblasts is not yet determined.
To identify the occurrence and the molecular mechanism of cell pyroptosis in skin fibroblasts, and explore the anti-pyroptotic effect of paeoniflorin in UVA induced photodamage protection.
Using Human skin fibroblasts (HSFs), wild-type primary human dermal fibroblasts (HDFs) and CASP3 knockdown HDFs, we analyzed the occurrence of pyroptosis by examining changes in morphology, LDH release and the expression of pyroptotic molecules after UVA radiation. UVA-exposed C57BL/6 mice and human sun-exposed skin samples were used to analyze the expression of caspase-3/GSDME. The role of oxidative stress was investigated by using NAC. Paeoniflorin treatment was analyzed for its effects on pyroptosis and the expression of caspase-3/GSDME.
Both HSFs and HDFs exposed to UVA exhibited dose-dependent pyroptosis. In HDFs, UVA increased the expression of caspase-3, GSDME, PARP, caspase-9, Cytochrome C, Bax/Bcl-2, while the expression of NLRP3, caspase-1, caspase-4, GSDMD was not significantly changed. UVA-exposed C57BL/6 mice and human sun-exposed skin samples showed increased caspase-3/GSDME. Treatment of NAC or paeoniflorin suppressed UVA-induced pyroptosis and mitochondrial-mediated apoptosis.
UVA induced caspase-3/GSDME mediated pyroptosis in both HSFs and HDFs, and paeoniflorin protected against UVA induced photodamage by suppressing this pathway.
紫外线A辐射可影响成纤维细胞并导致真皮结缔组织发生改变。细胞焦亡是一种程序性细胞死亡形式，其特征在于gasdermin介导的细胞膜孔形成和细胞内内容物释放。紫外线A照射是否能触发成纤维细胞焦亡尚不清楚。芍药苷具有抗氧化特性，但它是否通过抑制成纤维细胞中的氧化应激来减轻细胞焦亡尚未确定。
确定皮肤成纤维细胞中细胞焦亡的发生情况及其分子机制，并探讨芍药苷在紫外线A诱导的光损伤保护中的抗细胞焦亡作用。
使用人皮肤成纤维细胞（HSFs）、野生型原代人真皮成纤维细胞（HDFs）和Casp3基因敲低的HDFs，通过检测紫外线A辐射后形态变化、乳酸脱氢酶释放和细胞焦亡分子表达情况来分析细胞焦亡的发生。使用紫外线A照射的C57BL/6小鼠和人暴露于阳光下的皮肤样本分析caspase-3/GSDME的表达。通过使用NAC研究氧化应激的作用。分析芍药苷处理对细胞焦亡及caspase-3/GSDME表达的影响。
暴露于紫外线A的HSFs和HDFs均表现出剂量依赖性细胞焦亡。在HDFs中，紫外线A增加了caspase-3、GSDME、PARP、caspase-9、细胞色素C、Bax/Bcl-2的表达，而NLRP3、caspase-1、caspase-4、GSDMD的表达没有明显变化。紫外线A照射的C57BL/6小鼠和人暴露于阳光下的皮肤样本显示caspase-3/GSDME增加。NAC或芍药苷处理可抑制紫外线A诱导的细胞焦亡和线粒体介导的凋亡。
紫外线A在HSFs和HDFs中诱导caspase-3/GSDME介导的细胞焦亡，芍药苷通过抑制该途径保护免受紫外线A诱导的光损伤。
