Mechanism Of MiR-802-Hnf1b Signaling Axis In The Reduction Of Host Glucose Metabolism In Schistosoma Japonicum Infection

According to epidemiological study in rural China,individuals with a previous schistosome infection(PSI)show lower levels of adjusted fasting blood glucose,postprandial blood glucose,glycated hemoglobin A1c(Hb A1c)than individuals without a PSI.However,little is known about the mechanism between Schistosoma japonicum(S.japonicum)infection and glucose metabolism in the host.Here,miR-802 expression was significantly down-regulated in mice or patients infected with S.japonicum.miR-802 can bind to the 3'UTR of Hnf1 b to inhibit its translation.In vivo and in vitro experiments verified that Hnf1 b was remarkably up-regulated when miR-802 expression was reduced,leading to the phosphorylation of Akt at Thr308 and Ser473 and the improvement of insulin sensitivity in the host.Furthermore,we found that SEA treatment could enhance phosphorylation at Thr308 and Ser473 of Akt in the hepatocytes by down-regulating the expression of miR-802 and up-regulating the expression of Hnf1 b.Moreover,our study showed that S.japonicum infection decreased the level of miR-802 through affecting the immuno-microenvironment of the liver.S.japonicum infection led to down-regulation of NF-?B,while NF-?B did enhance the activity of the promoter of miR-802.And IL-4,IL-13,and their downstream STAT6 could inhibit the expression of miR-802.During the infection of S.japonicum,miR-802 could be directly influenced by SEA stimulation or suppressed by eggs-induced type 2 immune responses.Based on our data,Akt activation regulated by miR-802-Hnf1 b axis is involved in the metabolic modulation of S.japonicum infection on the host's glucose metabolism.Our results revealed an important regulatory role of miR-802 in the relationship between S.japonicum infection and host glucose metabolism,which might provide a novel therapeutic approach to treat some certain metabolic diseases.