Perivascular mesenchymal cells control adipose-tissue macrophage accrual in obesity.
Perivascular mesenchymal cells control adipose-tissue macrophage accrual in obesity.
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DOI：
10.1038/s42255-020-00301-7
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发表时间：
2020-11
影响因子：
20.8
通讯作者：
Gupta RK
中科院分区：
文献类型：
--
作者：
Shan B;Shao M;Zhang Q;Hepler C;Paschoal VA;Barnes SD;Vishvanath L;An YA;Jia L;Malladi VS;Strand DW;Gupta OT;Elmquist JK;Oh D;Gupta RK
慢性低度白色脂肪组织（WAT）炎症是肥胖代谢综合征的标志。在这里，我们证明了鼠WAT血管周围（PDGFRβ+）细胞亚群，称为“纤维炎性祖细胞”（FIP），在高脂饮食喂养开始后不久激活促炎信号级联反应，并以TLR 4依赖性方式调节WAT中促炎性巨噬细胞的积聚。肥胖症中FIPs的激活是通过ZFP 423的下调介导的，ZFP 423在此被鉴定为NFκB的转录共阻遏物。ZFP 423通过诱导p300到NuRD共调节子的转换来抑制NFκB的p65亚基的DNA结合能力。PDGFRβ+细胞中Zfp423的多西环素诱导表达抑制FIP中的炎症信号传导并减弱肥胖症中内脏WAT的代谢炎症PDGFRβ+细胞中Zfp423的诱导性失活增加FIP活性，加剧脂肪巨噬细胞积聚，并促进WAT功能障碍。这些研究暗示血管周围间充质细胞是肥胖症慢性脂肪组织炎症的重要调节因子，并将ZFP 423鉴定为NFκB信号传导的转录断裂。
Chronic low-grade white adipose tissue (WAT) inflammation is a hallmark of metabolic syndrome in obesity. Here, we demonstrate that a subpopulation of murine WAT perivascular (PDGFRβ+) cells, termed “fibro-inflammatory progenitors” (FIPs), activate pro-inflammatory signaling cascades shortly after the onset of high-fat diet feeding and regulate pro-inflammatory macrophage accumulation in WAT in a TLR4-dependent manner. FIPs activation in obesity is mediated by the downregulation of ZFP423, identified here as a transcriptional co-repressor of NFκB. ZFP423 suppresses the DNA-binding capacity of the p65 subunit of NFκB by inducing a p300 to NuRD co-regulator switch. Doxycycline-inducible expression of Zfp423 in PDGFRβ+ cells suppresses inflammatory signaling in FIPs and attenuates metabolic inflammation of visceral WAT in obesity. Inducible inactivation of Zfp423 in PDGFRβ+ cells increases FIP activity, exacerbates adipose macrophage accrual, and promotes WAT dysfunction. These studies implicate perivascular mesenchymal cells as important regulators of chronic adipose tissue inflammation in obesity and identify ZFP423 as a transcriptional break on NFκB signaling.
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影响因子：
16
作者：
Cardamone, M. Dafne;Krones, Anna;Tanasa, Bogdan;Taylor, Havilah;Ricci, Laura;Ohgi, Kenneth A.;Glass, Christopher K.;Rosenfeld, Michael G.;Perissi, Valentina
通讯作者：
Perissi, Valentina
巨噬细胞的局部扩散有助于与肥胖相关的脂肪组织炎症。
影响因子：
29
作者：
Amano SU;Cohen JL;Vangala P;Tencerova M;Nicoloro SM;Yawe JC;Shen Y;Czech MP;Aouadi M
通讯作者：
Aouadi M
影响因子：
--
作者：
Cho, Kae Won;Morris, David L.;Lumeng, Carey N.
通讯作者：
Lumeng, Carey N.
DOI：
10.1038/nrm3949
发表时间：
2015-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Heinz S;Romanoski CE;Benner C;Glass CK
通讯作者：
Glass CK
影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P