含patatin样磷脂酶结构域蛋白7通过过氧化物酶体增殖物激活受体γ促进巨噬细胞M2型极化  

The Patatin-like Phospholipase Domain Containing Protein 7(PNPLA7)Facilitates M2 Polarization of Macrophages Through a PPARγ-Dependent Mechanism

作　　者：王宇[1] 黄飞飞[1] 何晓红[1] 孙全[1] 常平安[1] WANG Yu;HUANG Fei-Fei;HE Xiao-Hong;SUN Quan;CHANG Ping-An(Chongqing Key Laboratory of Big Data for Bio-intelligence,College of Bio-information,Chongqing University of Posts and Telecommunications,Chongqing 400065,China)

机构地区：[1]重庆市大数据生物智能重点实验室重庆邮电大学生物信息学院,重庆400065

出　　处：《中国生物化学与分子生物学报》2022年第9期1193-1201,共9页Chinese Journal of Biochemistry and Molecular Biology

基　　金：Supported by Chongqing Innovation and Entrepreneurship Program for Returned Overseas Scholars(No.RC2020-2);Chongqing Natural Science Foundation(No.cstc2018jcyjAX0120,cstc2020jcyj-msxm X0007);National Natural Science Foundation of China(No.31801139)。

摘　　要：溶血磷脂酰胆碱(LPC)在免疫反应、组织炎症和重塑中调控巨噬细胞极化的动态和整体过程。含patatin样磷脂酶结构域蛋白7(PNPLA7)是近年发现的优先水解LPC的溶血磷脂酶。然而,直到现在仍不清楚PNPLA7在巨噬细胞极化中的表达和作用。本研究发现,PNPLA7在白细胞介素4(IL-4)刺激的巨噬细胞向替代激活(M2)表型的极化过程中上调(P<0.05)。本文发现,PNPLA7的敲低和过表达分别降低和增加了M2标记基因,包括精氨酸酶1(Arg1)和类几丁质酶3(Ym1)的表达(P<0.05)。进一步的研究表明,PNPLA7在M2极化过程中调节过氧化物酶体增殖物激活受体γ(PPARγ)在mRNA和蛋白质水平上的表达(P<0.05)。然而,信号转导和转录激活因子6(STAT6)的磷酸化不受PNPLA7的影响。这些发现表明,PNPLA7通过PPARγ相关机制促进巨噬细胞抗炎M2型极化。Lysophosphatidylcholine(LPC)modulates the dynamic and integral process of macrophage polarization in immune responses,tissue inflammation and remodeling.Patatin-like phospholipase domain containing protein 7(PNPLA7)was identified as an LPC-preferring lysophospholipase recently.However,the expression and role of PNPLA7 in macrophage polarization remained unknown.In the present study,PNPLA7 was found to be upregulated in the process of macrophage polarization toward an alternatively activated(M2)phenotype stimulated with interleukin 4(IL-4)(P<0.05).We found that knockdown and overexpression of PNPLA7 decreased and increased the expression of M2 marker genes,including arginase 1(Arg1)and chitinase-like 3(Ym1),respectively(P<0.05).Further studies showed that PNPLA7 regulated the expression of peroxisome proliferator activated receptor-γ(PPARγ)at the mRNA and protein levels during M2 polarization(P<0.05).However,the phosphorylation of signal transducer and activator of transcription 6(STAT6)was not influenced by PNPLA7.These findings suggest that PNPLA7 favors macrophage anti-inflammatory M2 polarization through a PPARγ-dependent mechanism.

关 键 词：M2巨噬细胞 溶血卵磷脂 含patatin样磷脂酶结构域蛋白7 过氧化物酶体增殖物激活受体Γ 

分 类 号：Q26[生物学—细胞生物学]