Investigation on the mechanism of simulated microgravity promoting rat cerebral angiogenesis based on proteomics

Abstract

Changed neurovascular homeostasis under microgravity may be closely related to the dysregulated angiogenesis resulting in neurovascular units and microvascular hyperpermeability. The present study aimed to investigate the mechanism of 7-day simulated microgravity (7d-SMG) promoting rat cerebral angiogenesis based on proteomics. 7d-SMG effect led to a slight inflammatory infiltration in rat cerebral cortex. The levels of oxidative stress, inflammatory factors, and pro-angiogenic factors were significantly increased. A total of 5499 proteins were detected by label-free quantitative proteomic strategy and 704 proteins were differentially expressed proteins (DEPs). 440 and 264 of DEPs were upregulated and downregulated, respectively. Gene-Ontology analysis suggested that most of DEPs were involved in brain development, actin cytoskeleton and filament organization, cell proliferation, which were closely associated with cerebral angiogenesis. The KEGG results showed that Rap1, Ras and other signaling pathways related to cell proliferation were significantly influenced by 7d-SMG. The expressions of VEGFR2, Crk, Rap1b, B-Raf, and the radio of pho-MEK/MEK, pho-ERK1/2/ERK1/2, Bcl2/Bax were respectively increased by 47.24 %, 25.11 %, 22.02 %, 41.44 %, 22.34 %, 24.87 %, 120.65 %, which indicated that 7d-SMG promoted cell proliferation through VEGFR2-Rap1b-ERK signaling pathway. The present study explored the effect of 7d-SMG regulating rat cerebral angiogenesis, which provided a novel insight to elucidate the potential mechanism of disrupted neurovascular homeostasis induced by MG. The expected results might benefit for maintaining nerve system health of astronauts during space flight.