Inhibition of NF-κB and Wnt/β-catenin/GSK3β Signaling Pathways Ameliorates Cardiomyocyte Hypertrophy and Fibrosis in Streptozotocin (STZ)-induced Type 1 Diabetic Rats.

Abstract

Type 1 diabetes mellitus (T1DM) is associated with an increased risk of diabetic cardiomyopathy (DCM). Nuclear factor kappa B (NF-κB) and Wnt/β-catenin/GSK3β have been demonstrated to play pathogenic roles in diabetes. In this study, we evaluated the roles of these two pathways in T1DM-induced cardiomyopathy in rats. Streptozotocin (STZ)-induced type 1 diabetic rats were treated with pyrrolidine dithiocarbamate (PDTC) or meisoindigo (Me) to inhibit NF-κB and Wnt/β-catenm/GSK3β respectively for 4 or 8 weeks. As compared with untreated diabetic rats, treatment with either PDTC or Me partly attenuated the myocardial hypertrophy and interstitial fibrosis, improved cardiac function, and exhibited reduction in inflammatory reaction. In addition, we found that inhibiting NF-κB and Wnt/β-catenin/GSK3β pathways could regulate glucose and lipid metabolism. The effects were associated with the decrease of NF-κB activity and the downregulation of some proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-2. Our data suggested that the activities of NF-κB and Wnt/β-catenin/GSK3β pathways were both increased and inhibiting NF-κB and Wnt/β-catenin/GSK3β signaling pathways might improve myocardial injury in T1DM rats.

• Authors: Jing-Jing Liu, Lu-Mei Shentu, Ning Ma, Li-Ying Wang, Gui-Min Zhang, Ying Sun, Yan Wang, Jun Li, Yan-Ling Mu
• Journal: Current medical science (Curr Med Sci) Vol. 40 Issue 1 Pg. 35-47 (Feb 2020) ISSN: 2523-899X [Electronic] China
• PMID: 32166663 (Publication Type: Journal Article)

Chemical References

• Indoles
• NF-kappa B
• Pyrrolidines
• Thiocarbamates
• pyrrolidine dithiocarbamic acid
• Streptozocin
• N-methylisoindigotin
• Glycogen Synthase Kinase 3 beta
• Gsk3b protein, rat

Topics

• Animals
• Diabetes Mellitus, Experimental (drug therapy, metabolism)
• Diabetes Mellitus, Type 2 (drug therapy, metabolism)
• Diabetic Cardiomyopathies (metabolism, prevention & control)
• Glycogen Synthase Kinase 3 beta (metabolism)
• Humans
• Indoles (administration & dosage, pharmacology)
• Lipid Metabolism (drug effects)
• Male
• Myocytes, Cardiac (cytology, drug effects, metabolism)
• NF-kappa B (metabolism)
• Pyrrolidines (administration & dosage, pharmacology)
• Rats
• Streptozocin
• Thiocarbamates (administration & dosage, pharmacology)
• Wnt Signaling Pathway (drug effects)