Journal of diabetes investigation
M1 macrophage-derived exosomes aggravate diabetic nephropathy by regulating the WTAP/S1PR2 axis
Por Li L, Liu H, Mao Y y 3 más.
Contenido en inglés
Resumen
Background
Diabetic nephropathy (DN) is a severe microvascular complication of diabetes mellitus. The specific role of M1 macrophage-derived exosomes in DN progression remains largely unexplored.
Methods
THP-1 monocytes were differentiated into M0 macrophages and polarized into M1 macrophages for exosome extraction. WTAP was silenced using shRNA to generate WTAP-deficient exosomes. Glomerular endothelial cells (GECs) were exposed to high glucose (HG) and co-incubated with modified exosomes. Cell viability, oxidative stress, apoptosis, barrier function, and angiogenic capacity were assessed. The WTAP-S1PR2 interaction was validated by RIP, MeRIP, and dual-luciferase assays. In vivo, db/db mice received tail vein injections of respective exosomes for 8 weeks, followed by assessments of renal function, histopathology, and inflammation.