Pharmacological HIF-1 activation upregulates extracellular vesicle production synergistically with adiponectin through transcriptional induction and protein stabilization of T-cadherin.

Scientific reports 2024 Feb 13

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Pharmacological 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. © 2024. The Author(s).

Citation

Kohei Fujii, Yuya Fujishima, Shunbun Kita, Keitaro Kawada, Keita Fukuoka, Taka-Aki Sakaue, Tomonori Okita, Emi Kawada-Horitani, Hirofumi Nagao, Shiro Fukuda, Norikazu Maeda, Hitoshi Nishizawa, Iichiro Shimomura. Pharmacological HIF-1 activation upregulates extracellular vesicle production synergistically with adiponectin through transcriptional induction and protein stabilization of T-cadherin. Scientific reports. 2024 Feb 13;14(1):3620