Aging Suppresses Sphingosine-1-Phosphate Chaperone ApoM in Circulation Resulting in Maladaptive Organ Repair.
Aging Suppresses Sphingosine-1-Phosphate Chaperone ApoM in Circulation Resulting in Maladaptive Organ Repair.
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DOI：
10.1016/j.devcel.2020.05.024
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发表时间：
2020-06-22
影响因子：
11.8
通讯作者：
Cao Z
中科院分区：
文献类型：
--
作者：
Ding BS;Yang D;Swendeman SL;Christoffersen C;Nielsen LB;Friedman SL;Powell CA;Hla T;Cao Z
Here we show that the liver-derived apolipoprotein M (ApoM) protects the lung and kidney from pro-fibrotic insults and that this circulating factor is attenuated in aged mice. Aged mouse hepatocytes exhibit transcriptional suppression of ApoM. This leads to reduced sphingosine-1-phosphate (S1P) signaling via the S1P receptor 1 (S1PR1) in the vascular endothelial cells of lung and kidney. Suboptimal S1PR1 angiocrine signaling causes reduced resistance to injury-induced vascular leak and leads to organ fibrosis. Plasma transfusion from Apom transgenic mice but not Apom knockout mice blocked fibrosis in the lung. Similarly, infusion of recombinant therapeutics, ApoM-Fc fusion protein enhanced kidney and lung regeneration and attenuated fibrosis in aged mouse after injury. Furthermore, we identified that aging alters Sirtuin1-hepatic nuclear factor 4α circuit in hepatocytes to downregulate ApoM. These data reveal an integrative organ adaptation that involves circulating S1P chaperone ApoM+HDL which signals via endothelial S1PR1 to spur regeneration over fibrosis.
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影响因子：
7.3
作者：
Galvani S;Sanson M;Blaho VA;Swendeman SL;Obinata H;Conger H;Dahlbäck B;Kono M;Proia RL;Smith JD;Hla T
通讯作者：
Hla T
年龄相关的 Sirtuin 1 血管平滑肌减少与血管衰老和炎症与腹主动脉瘤有关
影响因子：
20.1
作者：
Chen HZ;Wang F;Gao P;Pei JF;Liu Y;Xu TT;Tang X;Fu WY;Lu J;Yan YF;Wang XM;Han L;Zhang ZQ;Zhang R;Zou MH;Liu DP
通讯作者：
Liu DP
昼夜主义代谢的地图集揭示了时钟之间全系统的协调和通信。
影响因子：
64.5
作者：
Dyar KA;Lutter D;Artati A;Ceglia NJ;Liu Y;Armenta D;Jastroch M;Schneider S;de Mateo S;Cervantes M;Abbondante S;Tognini P;Orozco-Solis R;Kinouchi K;Wang C;Swerdloff R;Nadeef S;Masri S;Magistretti P;Orlando V;Borrelli E;Uhlenhaut NH;Baldi P;Adamski J;Tschöp MH;Eckel-Mahan K;Sassone-Corsi P
通讯作者：
Sassone-Corsi P
影响因子：
82.9
作者：
Cao Z;Lis R;Ginsberg M;Chavez D;Shido K;Rabbany SY;Fong GH;Sakmar TP;Rafii S;Ding BS
通讯作者：
Ding BS
影响因子：
4.8
作者：
Christoffersen, Christina;Jauhiainen, Matti;Nielsen, Lars Bo
通讯作者：
Nielsen, Lars Bo