ArticleFrontiers in physiology2025
Alteration of vasopressin-aquaporin system in hindlimb unloading mice.
Article in Frontiers in physiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Impact of Microgravity on Cytoskeletal Dynamics, Protein Transport, and Signaling Networks: Potential Therapeutic Opportunities for Skin Health.International journal of molecular sciences · 2026Review
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11 authors.
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Abstract
Murine hindlimb unloading (HU) is considered a model of choice for simulating the physiological effects of microgravity on several functions, including fluid and electrolyte homeostasis. Microgravity causes changes in blood redistribution, modulating vasopressin secretion, a major hormone controlling water reabsorption through the vasopressin-sensitive water channel AQP2. In this study, mice were hindlimb suspended over 4 weeks or rested in the ground as controls, and vasopressin levels, along with renal aquaporins expression were investigated. Copeptin, a stable precursor of the hormone vasopressin, significantly increased as early as 1 week of unloading which correlated with a significant increase in AQP2 total protein expression and decrease in serum osmolality, suggesting early activation of the vasopressin/AQP2 axis in this model. Conversely, in 4 weeks HU suspended mice, copeptin decreased significantly and both AQP2 mRNA and AQP2 total protein expression were significantly reduced. Consistent with a downregulation of the vasopressin/AQP2 axis an increase in serum osmolality was observed at 4 weeks HU. The basolateral water channels AQP3 and AQP4 were, on the other hand, unaffected. Immunolocalization studies confirmed reduced expression of AQP2 in renal collecting ducts of HU mice at 4 weeks. A significantly increased amount of the expressed AQP2 was found phosphorylated at Ser261, a site regulating AQP2 protein stability and degradation. In line, p38-MAPK, committed to phosphorylate Ser261 and to increase miR137 expression, an AQP2 mRNA-targeted microRNA, was significantly increased in HU, suggesting that reduced AQP2 expression was mainly due to increased protein degradation and downregulation of AQP2-mRNA translation. Our results suggest that vasopressin/AQP2 axis is upregulated as early as 1 week and may be involved in the antidiuretic response also observed in early spaceflight period in astronauts. Contrariwise, the vasopressin-AQP2 system is downregulated after 4 weeks HU, likely to counteract the persistent central venous pressure due to cephalic shift of fluids.
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