在合并糖尿病肾病的db/db小鼠以及培养的内皮细胞中,利拉鲁肽对Janus激酶/信号转导与转录激活因子(JAK/STAT)通路的影响

Translated title of the contribution: Effect of liraglutide on the Janus kinase/signal transducer and transcription activator (JAK/STAT) pathway in diabetic kidney disease in db/db mice and in cultured endothelial cells

Tali Zitman-Gal, Yael Einbinder, Meital Ohana, Aviva Katzav, Amany Kartawy, Sydney Benchetrit

Research output: Contribution to journalArticlepeer-review

Abstract

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 μg/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 μg/μL) 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.

Translated title of the contributionEffect of liraglutide on the Janus kinase/signal transducer and transcription activator (JAK/STAT) pathway in diabetic kidney disease in db/db mice and in cultured endothelial cells
Original languageChinese (Simplified)
Pages (from-to)656-664
Number of pages9
JournalJournal of Diabetes
Volume11
Issue number8
DOIs
StatePublished - Aug 2019

Keywords

  • JAK2
  • STAT3
  • db/db mice
  • diabetes
  • human umbilical vein endothelial cells
  • liraglutide

Fingerprint

Dive into the research topics of 'Effect of liraglutide on the Janus kinase/signal transducer and transcription activator (JAK/STAT) pathway in diabetic kidney disease in db/db mice and in cultured endothelial cells'. Together they form a unique fingerprint.

Cite this