Sun Yu, Li Jie, Li Yanhong, Wu Zhengli
College of Fisheries, Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Research Center of Fishery Resources and Environment, Southwest University, Chongqing 400715, China.
College of Fisheries, Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Research Center of Fishery Resources and Environment, Southwest University, Chongqing 400715, China.
Int J Biol Macromol. 2024 Sep 14;280(Pt 1):135647. doi: 10.1016/j.ijbiomac.2024.135647.
Peroxisome proliferator activated receptors (PPARs) exert their roles in lipid metabolism and adaptive immunity by transactivating carnitine palmitoyltransferase 1 (CPT1). However, it remains unclear whether the PPAR-CPT1 signaling pathway exists in mollusks that only carry out innate immunity. This study cloned and characterized PPAR and CPT1 genes from Hyriopsis cumingii for the first time, designated as HcPPARs and HcCPT1s, respectively. The bioinformatics analysis revealed conservative molecular characteristics of these genes across species. Real-time quantitative PCR results indicated that higher expression levels of HcPPARs and HcCPT1s in the blood, mantle, and intestine suggested their potential involvement in lipid metabolism and innate immunity of mollusks. Treatments with agonists and inhibitors demonstrated a correlation in the expression of HcPPARs and HcCPT1s. Dual luciferase reporter assay identified regions with high transcriptional activities on promoters of HcCPT1s and potential binding sites for HcPPARs through prediction and mutation sites. These results suggested that the PPAR-CPT1 signaling might exist in H. cumingii. This research provides a necessary foundation for exploring the role of the PPAR-CPT1 signaling in innate immunity, and offers new theoretical evidence for the molecular regulatory mechanism of mollusks and the treatment of metabolic disorders and inflammatory diseases.
过氧化物酶体增殖物激活受体（PPARs）通过反式激活肉碱棕榈酰转移酶1（CPT1）在脂质代谢和适应性免疫中发挥作用。然而，PPAR-CPT1信号通路是否存在于仅具有先天免疫的软体动物中仍不清楚。本研究首次从三角帆蚌中克隆并鉴定了PPAR和CPT1基因，分别命名为HcPPARs和HcCPT1s。生物信息学分析揭示了这些基因在物种间保守的分子特征。实时定量PCR结果表明，HcPPARs和HcCPT1s在血液、外套膜和肠道中的较高表达水平表明它们可能参与软体动物的脂质代谢和先天免疫。激动剂和抑制剂处理证明了HcPPARs和HcCPT1s表达之间的相关性。双荧光素酶报告基因检测通过预测和突变位点鉴定了HcCPT1s启动子上具有高转录活性的区域以及HcPPARs的潜在结合位点。这些结果表明PPAR-CPT1信号可能存在于三角帆蚌中。本研究为探索PPAR-CPT1信号在先天免疫中的作用提供了必要基础，并为软体动物的分子调控机制以及代谢紊乱和炎症性疾病的治疗提供了新的理论证据。
