ABSTRACT
Disulfide-bond A oxidoreductase-like protein (DsbA-L) is a molecular chaperone involved in the multimerization of adiponectin. Recent studies have found that DsbA-L is related to metabolic diseases including gestational diabetes mellitus (GDM), and can be regulated by peroxisome proliferator-activated receptor γ (PPARγ) agonists; the specific mechanism, however, is uncertain. Furthermore, the relationship between DsbA-L and the novel adipokine chemerin is also unclear. This article aims to investigate the role of DsbA-L in the improvement of insulin resistance by PPARγ agonists in trophoblast cells cultured by the high-glucose simulation of GDM placenta. Immunohistochemistry and western blot were used to detect differences between GDM patients and normal pregnant women in DsbA-L expression in the adipose tissue. The western blot technique was performed to verify the relationship between PPARγ agonists and DsbA-L, and to explore changes in key molecules of the insulin signaling pathway, as well as the effect of chemerin on DsbA-L. Results showed that DsbA-L was significantly downregulated in the adipose tissue of GDM patients. Both PPARγ agonists and chemerin could upregulate the level of DsbA-L. Silencing DsbA-L affected the function of rosiglitazone to promote the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (PKB)/AKT pathway. Therefore, it is plausible to speculate that DsbA-L is essential in the environment of PPARγ agonists for raising insulin sensitivity. Overall, we further clarified the mechanism by which PPARγ agonists improve insulin resistance.
ABSTRACT
The relationship between T cell immunoglobulin domain and mucin domain protein 3 (Tim-3)/Galectin (Gal)-9 pathway and recurrent spontaneous abortion (RSA) was studied. Thirty-one pregnant women with RSA and 27 normal early gravidas were investigated to detect the levels of Tim-3 and Gal-9 in villi and deciduas by Western blotting. Meanwhile, the concentration of interleukin (IL)-4 and IL-12 in peripheral blood plasma was determined by ELISA in 25 healthy fertile non-pregnant controls, the normal early gravidas and pregnant women with RSA mentioned above, respectively. It was found that the relative expression levels of Tim-3 and Gal-9 in villi and deciduas were significantly increased in pregnant women with RSA as compared with those in the normal early gravidas. The concentration of IL-4 in peripheral blood plasma of pregnant women with RSA was lower than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05), but that of IL-2 in pregnant women with RSA was significantly higher than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05). It was suggested that the overexpression of Tim-3/Gal-9 pathway may be related to the pathogenesis of RSA.
ABSTRACT
The relationship between T cell immunoglobulin domain and mucin domain protein 3 (Tim-3)/Galectin (Gal)-9 pathway and recurrent spontaneous abortion (RSA) was studied. Thirty-one pregnant women with RSA and 27 normal early gravidas were investigated to detect the levels of Tim-3 and Gal-9 in villi and deciduas by Western blotting. Meanwhile, the concentration of interleukin (IL)-4 and IL-12 in peripheral blood plasma was determined by ELISA in 25 healthy fertile non-pregnant controls, the normal early gravidas and pregnant women with RSA mentioned above, respectively. It was found that the relative expression levels of Tim-3 and Gal-9 in villi and deciduas were significantly increased in pregnant women with RSA as compared with those in the normal early gravidas. The concentration of IL-4 in peripheral blood plasma of pregnant women with RSA was lower than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05), but that of IL-2 in pregnant women with RSA was significantly higher than that of the normal early gravidas (P<0.05) and healthy fertile non-pregnant controls (P<0.05). It was suggested that the overexpression of Tim-3/Gal-9 pathway may be related to the pathogenesis of RSA.