C3a/C3aR axis is involved in diabetic kidney injury by regulating podocyte mitophagy in diabetic nephropathy.

ABSTRACT: The C3a/C3aR axis has been confirmed to be associated with the pathogenesis of diabetic nephropathy (DN) and mitochondrial dysfunction; however, the exact mechanisms underlying its role in diabetic podocytopathy remain unclear. The present study investigated the involvement of C3a/C3aR signaling in regulating mitophagy during the progression of DN. Diabetic db/db mice exhibited elevated renal C3 and C3aR levels, concurrent with podocyte injury, proteinuria and glomerular damage. Administration of the C3aR antagonist (C3aRA) SB290157 attenuated podocyte loss, reduced albuminuria and mitigated glomerular pathology. Ultrastructural and functional analyses revealed that C3aRA restored mitochondrial integrity in podocytes, resolving diabetes‑associated fragmentation and bioenergetic deficits. I

SUBMITTER: Weng M 

PROVIDER: S-EPMC12549072 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature