RAGE Regulating Vascular Remodeling in Diabetes by Regulating Mitochondrial Dynamics with JAK2/STAT3 Pathway

Area of Science:

• Cardiovascular Research
• Endocrinology
• Cell Biology

Background:

• Vascular remodeling is a significant complication of diabetes.
• The Receptor for Advanced Glycation End products (RAGE) is implicated in inflammatory processes.
• Mitochondrial dynamics play a role in cellular health and disease.

Purpose of the Study:

• To investigate the role of mitochondrial dynamics in diabetes-induced vascular remodeling.
• To explore the modulation of these processes by the Receptor for Advanced Glycation End products (RAGE).

Main Methods:

• Utilized cellular and animal models of Type 2 diabetes.
• Measured expression of RAGE, JAK2/STAT3 signaling, TRPM channels, and DRP1.
• Employed western blotting and immunofluorescence in vitro and in vivo.
• Assessed effects of RAGE inhibition and STAT3/DRP1 suppression on vascular smooth muscle cells (VSMCs).

Main Results:

• Elevated RAGE, p-JAK2, p-STAT3, TRPM, and p-DRP1 were observed in diabetic models.
• RAGE inhibition significantly decreased the expression of these proteins.
• Suppressing STAT3 and DRP1 phosphorylation mimicked RAGE inhibition effects on VSMC proliferation, migration, and invasion.

Conclusions:

• RAGE regulates vascular remodeling in diabetes through modulation of mitochondrial dynamics via the JAK2/STAT3 axis.
• Findings enhance understanding of diabetic vascular disease pathology.
• Provides a theoretical basis for novel therapeutic targets for diabetic cardiovascular complications.