Journal
JOURNAL OF DIABETES
Volume 11, Issue 8, Pages 656-664Publisher
WILEY
DOI: 10.1111/1753-0407.12891
Keywords
db; db mice; diabetes; human umbilical vein endothelial cells; JAK2; liraglutide; STAT3
Categories
Funding
- Israeli Society of Nephrology and Hypertension
Ask authors/readers for more resources
Background Emerging evidence demonstrates the involvement of Janus tyrosine kinase/signal transducer and transcription activator (JAK/STAT) proteins in the pathophysiology of diabetic kidney disease (DKD). The JAK/STAT pathway is involved in the inflammatory response and endothelial cell dysfunction observed in DKD. The glucagon-like peptide-1 (GLP-1) analog liraglutide is an effective treatment for type 2 diabetes because it improves the inflammatory changes observed in experimental models of DKD. This study used db/db mice and endothelial cells (ECs) to determine the effect of diabetic environment on the JAK/STAT pathway and to assess the potential effect of liraglutide (200 mu g/kg) in both models. Methods Diabetic db/db mice (12 weeks old) were treated with liraglutide for 14 weeks. The kidneys were then perfused with saline and removed for mRNA, protein, and immunohistochemical analyses. Endothelial cells were stimulated advanced glycation end products (AGEs) (200 mu g/mu L) glucose (200 mg/dL) and liraglutide (100 nM) for 24 hours. Total RNA and protein were extracted and analyzed for expression of JAK/STAT signaling. Results Phosphorylated (p-) STAT3 was significantly upregulated in db/db mice compared with non-diabetic mice. Liraglutide significantly downregulated p-STAT3 protein expression in db/db mice. In db/db mice, p-STAT3 was primarily expressed in the glomeruli, whereas p-JAK2 was also expressed in kidney tubules. In ECs, liraglutide treatment prevented increased expression of p-STAT3 and p-JAK2. Liraglutide inhibited the target gene suppressor of cytokine signaling 3 (SOCS3) and sirtuin 1 (SIRT1) in db/db mice and in cultured EC. Conclusions This study suggests that the GLP-1 analog liraglutide inhibits the JAK/STAT pathway, which participates in intracellular processes in experimental models of diabetes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available