| First Author | Ding BS | Year | 2020 |
| Journal | Dev Cell | Volume | 53 |
| Issue | 6 | Pages | 677-690.e4 |
| PubMed ID | 32544390 | Mgi Jnum | J:290844 |
| Mgi Id | MGI:6437596 | Doi | 10.1016/j.devcel.2020.05.024 |
| Citation | Ding BS, et al. (2020) Aging Suppresses Sphingosine-1-Phosphate Chaperone ApoM in Circulation Resulting in Maladaptive Organ Repair. Dev Cell 53(6):677-690.e4 |
| abstractText | 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 Sirtuin-1-hepatic nuclear factor 4alpha circuit in hepatocytes to downregulate ApoM. These data reveal an integrative organ adaptation that involves circulating S1P chaperone ApoM(+) high density lipoprotein (HDL), which signals via endothelial niche S1PR1 to spur regeneration over fibrosis. |
