Key Laboratory of the Ministry of Education, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, and Chongqing Key Laboratory of Child Infections and Immunity, Chongqing, China (mainland).
Department of Nephrology, Children's Hospital of Chongqing Medical University, Chongqing, China (mainland).
Med Sci Monit. 2018 Sep 27;24:6832-6839. doi: 10.12659/MSM.909810.
BACKGROUND CD36 plays a critical role in many sterile inflammatory diseases, including type 2 diabetes mellitus, atherosclerosis, and primary nephrotic syndrome. This study investigated whether CD36 activates the nucleotide-binding domain leucine-rich repeat-containing family, pyrin domain-containing-3 (NLRP3) inflammasome and promotes podocytes apoptosis in primary nephrotic syndrome. MATERIAL AND METHODS The mouse podocyte cell line MPC5 was used as a model. mRNA and protein expression of CD36 and NLRP3 was quantified by real-time PCR and Western blotting, respectively. Levels of caspase-1 activity and total cholesterol were determined using commercial kits. Intracellular lipid droplets were detected by Oil Red O staining. CD36 expression was also examined in nephrotic mouse kidney tissue by immunohistochemistry and immunofluorescence. Intracellular lipid droplet was examined by Oil Red O staining. RESULTS CD36 expression was increased in nephrotic mouse kidney tissue. Treatment with interleukin-1b increased expression of CD36 and total cholesterol in MPC5 cells. Moreover, this treatment increased expression of NLRP3 and the percentage of apoptotic cells, both of which were inhibited by co-treatment with an anti-CD36 antibody. CONCLUSIONS CD36 might play an important role in podocyte apoptosis by activating the NLRP3 inflammasome in primary nephrotic syndrome.
CD36 在许多无菌性炎症性疾病中发挥着关键作用，包括 2 型糖尿病、动脉粥样硬化和原发性肾病综合征。本研究旨在探讨 CD36 是否通过激活核苷酸结合域富含亮氨酸重复序列家族、pyrin 结构域包含蛋白 3（NLRP3）炎性体并促进原发性肾病综合征中的足细胞凋亡。
使用小鼠足细胞系 MPC5 作为模型。通过实时 PCR 和 Western blot 分别定量 CD36 和 NLRP3 的 mRNA 和蛋白表达。使用商业试剂盒测定半胱氨酸天冬氨酸蛋白酶-1（caspase-1）活性和总胆固醇水平。用油红 O 染色检测细胞内脂滴。通过免疫组织化学和免疫荧光染色检测肾病小鼠肾脏组织中 CD36 的表达。用油红 O 染色检测细胞内脂滴。
肾病小鼠肾脏组织中 CD36 的表达增加。白细胞介素-1β处理增加了 MPC5 细胞中 CD36 和总胆固醇的表达。此外，这种处理增加了 NLRP3 的表达和凋亡细胞的比例，而用抗 CD36 抗体共同处理则抑制了这两种作用。
在原发性肾病综合征中，CD36 通过激活 NLRP3 炎性体可能在足细胞凋亡中发挥重要作用。
