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Complement 5a receptor 2 attenuates diabetic kidney disease by promoting mitochondria-associated endoplasmic reticulum membrane formation mediated by PSS-MFN2 interaction - PubMed

6 hours ago
  • #Mitochondria-Associated ER Membrane
  • #Complement Receptor
  • #Diabetic Kidney Disease
  • C5aR2 expression increases in diabetic kidney disease (DKD) patients and correlates with disease severity.
  • C5aR2 deficiency in diabetic mice worsens DKD, causing lipid accumulation and organelle dysfunction.
  • C5aR2 activates c-FOS, upregulates phosphatidylserine synthase (PSS), and promotes PSS-MFN2 interaction.
  • This interaction enhances mitochondria-associated ER membrane (MAM) formation and phosphatidylserine (PS) biosynthesis.
  • C5aR2 agonist P59 improves DKD, PS homeostasis, and MAM formation, reversing lipid and organelle dysfunction.
  • Single-cell RNA-seq shows P59 restores Pss expression in injured proximal tubular cells in mice.
  • C5aR2 activation is highlighted as a promising therapeutic strategy for DKD.