Aging Suppresses Sphingosine-1-Phosphate Chaperone ApoM in Circulation Resulting in Maladaptive Organ Repair
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Standard
Aging Suppresses Sphingosine-1-Phosphate Chaperone ApoM in Circulation Resulting in Maladaptive Organ Repair. / Ding, Bi Sen; Yang, Dawei; Swendeman, Steve L.; Christoffersen, Christina; Nielsen, Lars B.; Friedman, Scott L.; Powell, Charles A.; Hla, Timothy; Cao, Zhongwei.
I: Developmental Cell, Bind 53, Nr. 6, 2020, s. 677-690.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Aging Suppresses Sphingosine-1-Phosphate Chaperone ApoM in Circulation Resulting in Maladaptive Organ Repair
AU - Ding, Bi Sen
AU - Yang, Dawei
AU - Swendeman, Steve L.
AU - Christoffersen, Christina
AU - Nielsen, Lars B.
AU - Friedman, Scott L.
AU - Powell, Charles A.
AU - Hla, Timothy
AU - Cao, Zhongwei
PY - 2020
Y1 - 2020
N2 - 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 4α 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.
AB - 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 4α 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.
KW - aging
KW - endothelial cell
KW - fibrosis
KW - kidney repair
KW - lipoprotein
KW - lung regeneration
KW - sphingosine-1-phosphate receptor
KW - vascular barrier
KW - vascular niche
UR - http://www.scopus.com/inward/record.url?scp=85086602840&partnerID=8YFLogxK
U2 - 10.1016/j.devcel.2020.05.024
DO - 10.1016/j.devcel.2020.05.024
M3 - Journal article
C2 - 32544390
AN - SCOPUS:85086602840
VL - 53
SP - 677
EP - 690
JO - Developmental Cell
JF - Developmental Cell
SN - 1534-5807
IS - 6
ER -
ID: 244527597