Molecular Mechanisms Of P38 MAPK And Insulin Signaling Pathways In Regulating The Response To Simulated Microgravity In C.elegans

In view of the high cost,long cycle,and difficulty in carrying out space flight experiments,the simulated microgravity effects on the ground using biological models have received great attention.The p38 MAPK signaling pathway is a highly conserved signaling pathway in eukaryotes,and plays an important role in the regulation of stress response in C.elegans.Insulin signaling pathway is important in regulating the lifespan,growth,and development of C.elegans.However,the molecular mechanism of p38 MAPK and insulin signaling pathways in regulating simulated microgravity is still largely unclear.This study aimed to investigate the molecular mechanisms of p38 MAPK signaling and insulin signaling pathways in regulating simulated microgravity in nematodes.Simulated microgravity significantly increased the transcriptional expression of the genes encoding the p38 MAPK signaling pathway(pmk-1?sek-1 and nsy-1)and the protein expression of phosphorylation of PMK-1/p38 MAPK in nematodes.The pmk-1?sek-1 and nsy-1 mutant showed susceptibility to simulated microgravity compared to wild-type nematodes.The intestinal specific activity of PMK-1 was required for the regulation of response to simulated microgravity,and the entire p38 MAPK signaling pathway acted in intestine cells to regulate the response to simulated microgravity.In intestinal cells,two transcription factors,SKN-1 and ATF-7,acted as downstream targets of PMK-1 in regulating the response to simulated microgravity.Simulated microgravity significantly reduced the transcriptional expression of daf-2,age-1,and akt-1,and increased the transcriptional expression of daf-16 in the insulin signaling pathway.Compared to wild-type nematodes,daf-2,age-1,or akt-1 mutant showed resistance to simulated microgravity;however daf-16 mutant showed susceptibility to simulated microgravity.The insulin signaling pathway acted in intestine cells to regulate the response to simulated microgravity.In intestine cells,LYS-7 and SODH-1 acted as downstream targets of the transcription factor DAF-16 to regulate the response to simulated microgravity.In conclusion,activation of p38 MAPK or insulin signaling may mediate the protective mechanism for nematodes against the adverse effects of simulated microgravity.This study will deepen our understanding the molecular mechanisms underlying for the response of animals to simulated microgravity.