Nrf2 alleviates spaceflight-induced immunosuppression and thrombotic microangiopathy in mice

Abstract

Spaceflight-related stresses impact health via various body systems, including the haematopoietic and immune systems, with effects ranging from moderate alterations of homoeostasis to serious illness. Oxidative stress appears to be involved in these changes, and the transcription factor Nrf2, which regulates expression of a set of cytoprotective and antioxidative stress response genes, has been implicated in the response to spaceflight-induced stresses. Here, we show through analyses of mice from the MHU-3 project, in which Nrf2-knockout mice travelled in space for 31 days, that mice lacking Nrf2 suffer more seriously from spaceflight-induced immunosuppression than wild-type mice. We discovered that a one-month spaceflight-triggered the expression of tissue inflammatory marker genes in wild-type mice, an effect that was even more pronounced in the absence of Nrf2. Concomitant with induction of inflammatory conditions, the consumption of coagulation-fibrinolytic factors and platelets was elevated by spaceflight and further accelerated by Nrf2 deficiency. These results highlight that Nrf2 mitigates spaceflight-induced inflammation, subsequent immunosuppression, and thrombotic microangiopathy. These observations reveal a new strategy to relieve health problems encountered during spaceflight.

Upregulation of Amy1 in the salivary glands of mice exposed to a lunar gravity environment using the multiple artificial gravity research system

“…Artificial lunar gravity was developed using multiple artificial gravity research systems (MARS) that use a centrifuge to create artificial gravity, enabling comparative studies between the effects of gravity and microgravity in space ( Shimbo et al, 2016 ; Shiba et al, 2017 ; Okada et al, 2021 ). This system has contributed to analysis of sulfur metabolomic and transcriptomic changes in the liver ( Kurosawa et al, 2021 ), metabolic effects in adipose tissues ( Suzuki et al, 2020 ; Uruno et al, 2021 ), blood parameters changes ( Shimizu et al, 2023 ), bone mineralization, blood pressure, and lipid metabolism in mouse kidneys ( Suzuki et al, 2022 ) during space travel. This study investigated the basic foundations for oral clinical medicine under lunar gravity.…”

Cosmic kidney disease: an integrated pan-omic, physiological and morphological study into spaceflight-induced renal dysfunction

“…Figure 4c ; Supplementary Fig. 7 ; Supplementary Data 5 ) Rat data at request of CNSA authors (10.3389/fphys.2020.00939), MHU-3 data at request from authors ( https://ibsls.megabank.tohoku.ac.jp/metabolite-list ) 70 , 71 , NASA OSDR : OSD-571 (10.26030/h3p5-tc29) Fig. 6c ) data available from Peptide Atlas ( https://peptideatlas.org/ ).…”