Liraglutide Regulates the Kidney and Liver in Diabetic Nephropathy Rats through the miR-34a/SIRT1 Pathway.

PURPOSE: To explore the regulatory effects of liraglutide on the kidney and liver through the miR-34a/SIRT1 pathway with related factors in diabetic nephropathy (DN) rats. METHODS: DN rats were randomly divided into two groups (n = 10) and were injected with liraglutide or normal saline twice a day. The 24-hour urine microalbumin content and biochemical index levels were measured. qRT-PCR was performed to detect the expression of miR-34a in the kidney and liver tissues. The levels of SIRT1, HIF-1a, Egr-1, and TGF-ß1 in kidney and liver tissues were determined using qRT-PCR, western blot, and immunohistochemistry. Electron microscopy and HE staining were used to observe the ultrastructure and pathological changes. RESULTS: Liraglutide treatment in DN rats decreased blood glucose, 24-hour urine microalbumin, TC, TG, LDL-C, UA, Cr, UREA, ALT, and AST levels and increased the level of HDL-C (P < 0.05). Compared with the control group, the miR-34a levels were significantly decreased in kidney and liver tissues followed by liraglutide treatment (P < 0.05). The levels of SIRT1 in the liraglutide group are significantly higher than those in the control group with the kidney and liver tissues (P < 0.05). Conversely, the contents of HIF-1a, Egr-1, and TGF-ß1 were significantly lower in the liraglutide group than in the control group (P < 0.05). Electron microscopy showed that the kidney of the liraglutide-treated group exhibited minor broadening of the mesangial areas, fewer deposits, and a well-organized foot process. HE staining revealed that the kidney of the liraglutide-treated rats had a more regular morphology of the glomerulus and Bowman sac cavity and lighter tubular edema. Additionally, the liraglutide-treated DN rats had a clear hepatic structure, a lower degree of steatosis, and mild inflammatory cell infiltration. CONCLUSION: Liraglutide, through its effect on the miR-34a/SIRT1 pathway, may have a protective role in the kidney and liver of DN rats.

Identification of ß-chain of Fo F1 -ATPase in apoptotic cell population induced by Microplitis bicoloratus bracovirus and its role in the development of Spodoptera litura.

Two physiological changes of Spodoptera litura parasitized by Microplitis bicoloratus are hemocyte-apoptosis and retarded immature development. ß-Chain of Fo F1 -ATPase was found from a S. litura transcriptome. It belongs to a conserved P-loop NTPase superfamily, descending from a common ancestor of Lepidopteran clade. However, the characterization of ß-chain of ATPase in apoptotic cells and its involvement in development remain unknown. Here, the ectopic expression and endogenous Fo F1 -ATPase ß-chain occurred on S. litura cell membrane: in vivo, at the late stage of apoptotic hemocyte, endogenous Fo F1 -ATPase ß-chain was stably expressed during M. bicoloratus larva development from 4 to 7 days post-parasitization; in vitro, at an early stage of pre-apoptotic Spli221 cells by infecting with M. bicoloratus bracovirus particles, the proteins were speedily recover expression. Furthermore, endogenous Fo F1 -ATPase ß-chain was localized on the apoptotic cell membrane. RNA interference (RNAi) of Fo F1 -ATPase ß-chain led to significantly decreased head capsule width. This suggested that Fo F1 -ATPase ß-chain positively regulated the development of S. litura. The RNAi effect on the head capsule width was enhanced with parasitism. Our research found that Fo F1 -ATPase ß-chain was expressed and localized on the cell membrane in the apoptotic cells, and involved in the development of S. litura.