ABSTRACT
Type 2 diabetes mellitus (T2DM) is a metabolic disease with an increasing incidence worldwide, which leads to damage to various tissues and organs including the liver. MiR-31 is conserved across species and closely associated with metabolic diseases, but its role in type 2 diabetic liver injury has not been elucidated. This study aimed to investigate the effect of miR-31 on liver injury in type 2 diabetes and its underlying mechanism. Four to six weeks old male FVB mice and miR-31-positive transgenic mice were randomly divided into FVB mice control group (C), FVB mice induced diabetes group (DM) and miR-31-overexpression transgenic mice induced diabetes group (31DM). After 1 week of adaptive feeding, the T2DM mouse model was induced by high-fat feeding combined with intraperitoneal injection of streptozotocin (STZ) for 6 weeks. The general condition of mice and related metabolic indicators showed that the increased food and water intake, weight loss and glucose and lipid metabolism disorders could be reversed by miR-31 in T2DM mice. HE staining and liver histological activity index (HAI) scoring results showed that miR-31 improved the inflammatory status in the liver tissue of T2DM mice and decreased the HAI score. RT-qPCR results showed that the high expression of miR-31 was accompanied by a decrease in the expression of activating transcription factor 6 (ATF6) mRNA in the liver of T2DM mice. Furthermore, Western blotting results showed that miR-31 inhibited the expression of endoplasmic reticulum stress-related proteins such as ATF6, glucoregulatory protein 78 (GRP78) and C/EBP homologous protein (CHOP) in the liver of T2DM mice. In conclusion, miR-31 may ameliorate liver injury in T2DM mice by regulating glucose and lipid metabolism disorders and insulin resistance, and inhibiting endoplasmic reticulum stress factors such as ATF6, GRP78, and CHOP.
ABSTRACT
Objective To study the effect of human umbilical cord mesenchymal stem cells (hUCMSCs) tail vein transplantation on depressive behavior in chronic unpredictable mild stress (CUMS) model mice. Methods The third generation hUCMSCs were abtained; Sixty C57BL/6 male mice were randomly divided into the normal model group (+ normal saline), the cell group (+hUCMSCs) and the fluoxetine(flu) group (+flu), with 15 mice in each group. The depression model of CUMS mice with a 6 week duration was constructed; From the third week, hUCMSCs and normal saline were transplanted into the mice by tail vein injection, and the mice were gavaged with flu daily from the fifth week; Weight changes in each group were recorded weekly; The depression model and therapeutic effect of mice were evaluated by sucrose preference test, tail suspension test, forced swimming test and open field test; The cell changes of CAI and CA3 region in hippocampus were observed by HE staining; Transmission electron microscopy was used to detect the changes of synapses in CA3 region of hippocampus; Real-time PCR was used to detect mRNA expressions of synaphysin (SYP) and postsynaptic density protein 95 (PSD-95), which are key proteins of synaptic plasticity. Results hUCMSCs improved weight decrease in depressed mice; behavioral experiments observed that the model group mice showed depressive behavior, while the cell group and the drug group mice depression were improved; HE staining showed that, compared with the model group, cells in CA 1 and CA3 regions of the hippocampus of mice in the cell group and the group were arranged orderly and the number of cells increased; Transmission electron microscopy showed that compared with the model group, the number of synapses in the CA3 region of the hippocampus was more, the synaptic gap was narrower, and the density of synaptic spines was higher in the cell group and the drug group; More mRNA expressions of SYP and PSD-95 were detected by Real-time PCR in the cell group and the drug group than in the model group. Conclusion hUCMSCs transplatation showes antidepressant effects, which are associated with improved synaptic plasticity in the hippocampus.