Author:
Fujii Kohei,Fujishima Yuya,Kita Shunbun,Kawada Keitaro,Fukuoka Keita,Sakaue Taka-aki,Okita Tomonori,Kawada-Horitani Emi,Nagao Hirofumi,Fukuda Shiro,Maeda Norikazu,Nishizawa Hitoshi,Shimomura Iichiro
Abstract
AbstractPharmacological activation of hypoxia-inducible factor 1 (HIF-1), a hypoxia-responsive transcription factor, has attracted increasing attention due to its efficacy not only in renal anemia but also in various disease models. Our study demonstrated that a HIF-1 activator enhanced extracellular vesicle (EV) production from cultured endothelial cells synergistically with adiponectin, an adipocyte-derived factor, through both transcriptional induction and posttranscriptional stabilization of an adiponectin binding partner, T-cadherin. Increased EV levels were observed in wild-type mice but not in T-cadherin null mice after consecutive administration of roxadustat. Adiponectin- and T-cadherin-dependent increased EV production may be involved in the pleiotropic effects of HIF-1 activators.
Funder
Grants-in-Aid for Scientific Research
Bayer Scholarship for Cardiovascular Research
Manpei Suzuki Diabetes Foundation
Suzuken Memorial Foundation
Japan Association of Medical Research and Development
MSD Life Science Foundation, Public Interest Incorporated Foundation
Publisher
Springer Science and Business Media LLC