Dong Zhonghua, Li Xiao, Wang Xuan, Xu Jingya, Xu Wei
Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Engineering and Technology Research Center for Pediatric Drug Development, Shandong Medicine and Health Key Laboratory of Clinical Pharmacy, 16766 Jingshi Road, Jinan 250014, China.
College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
Food Funct. 2025 Aug 11;16(16):6599-6611. doi: 10.1039/d5fo00371g.
: Diabetic kidney disease (DKD), a common microvascular complication of diabetes mellitus, is recognized as a leading cause of end-stage renal disease. Ergosterol, a natural sterol abundant in edible fungi, has shown pharmacological effects that may benefit DKD treatment. However, its precise mechanisms of action remain elusive. This study aimed to evaluate the therapeutic efficacy of ergosterol in DKD and to delineate the underlying mechanisms. : Transcriptome microarray sequencing data from DKD patients retrieved from the public GEO database, as well as data from mouse DKD models, were analyzed to identify differentially expressed genes. Db/db mouse, high-glucose-induced HK-2 cells and conditioned THP-1 cells were employed to evaluate the impact of ergosterol on renal function, lipid metabolism, and macrophage phenotypic transformation. : Transcriptional profiling of DKD kidneys revealed alterations in fatty acid metabolism, which were corroborated in db/db mice. Ergosterol significantly improved renal function, reduced lipid accumulation, and mitigated inflammation. CPT1A, a key modulator of fatty acid metabolism, was identified as a target. The inhibition of CPT1A in renal tubular epithelial cells led to impaired fatty acid oxidation and lipid accumulation. Excessive renal lipids further stimulated macrophages to transform into pro-inflammatory phenotypes, leading to renal inflammation infiltration and exacerbating kidney damage. Ergosterol upregulated CPT1A expression through transcriptional regulation of FOXA1, thereby reducing lipid accumulation and subsequent renal inflammation. : Ergosterol enhances renal fatty acid oxidation the FOXA1/CPT1A pathway, reducing renal lipid accumulation and inflammation, potentially delaying DKD progression. This study elucidates the therapeutic potential of ergosterol in DKD therapy and provides new insights into the treatment of this disease.
糖尿病肾病（DKD）是糖尿病常见的微血管并发症，被认为是终末期肾病的主要病因。麦角固醇是一种在食用菌中含量丰富的天然固醇，已显示出可能有益于DKD治疗的药理作用。然而，其确切的作用机制仍不清楚。本研究旨在评估麦角固醇对DKD的治疗效果，并阐明其潜在机制。：分析从公共GEO数据库检索到的DKD患者的转录组微阵列测序数据，以及来自小鼠DKD模型的数据，以鉴定差异表达基因。使用db/db小鼠、高糖诱导的HK-2细胞和条件性THP-1细胞来评估麦角固醇对肾功能、脂质代谢和巨噬细胞表型转化的影响。：DKD肾脏的转录谱分析揭示了脂肪酸代谢的改变，这在db/db小鼠中得到了证实。麦角固醇显著改善肾功能，减少脂质积累，并减轻炎症。脂肪酸代谢的关键调节因子CPT1A被确定为一个靶点。肾小管上皮细胞中CPT1A的抑制导致脂肪酸氧化受损和脂质积累。过多的肾脏脂质进一步刺激巨噬细胞转化为促炎表型，导致肾脏炎症浸润并加剧肾脏损伤。麦角固醇通过FOXA1的转录调控上调CPT1A表达，从而减少脂质积累和随后的肾脏炎症。：麦角固醇通过FOXA1/CPT1A途径增强肾脏脂肪酸氧化，减少肾脏脂质积累和炎症，可能延缓DKD的进展。本研究阐明了麦角固醇在DKD治疗中的治疗潜力，并为该疾病的治疗提供了新的见解。
