- Academic Editor
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†These authors contributed equally.
Background: Renin-dependent hypertension with tubulointerstitial injury
remains a problem with high prevalence in the clinic. However, whether and how
renin participates in tubulointerstitial injury remains incompletely understood.
New evidence suggests that renin cleaves C3 into C3a and C3b. In the present
study, we aimed to explore the role of renin-mediated C3a/C3a receptor (C3aR)
signaling in renin-dependent hypertension-induced kidney injury and illustrate
the detailed mechanisms. Methods: C3a concentration changes in serum
from healthy volunteers incubated with recombinant renin were detected by ELISA.
C3aR expression in human tubular epithelial cells was evaluated in renal biopsy
sections from malignant arteriolonephrosclerosis and benign
arteriolonephrosclerosis patients. C3aR changes in human kidney 2 (HK2) cells
were detected after the cells were treated with human serum, renin and aliskiren.
The C3a analogue and C3aR antagonist SB290157 were used to stimulate HK2 cells to
explore the downstream signaling of C3a/C3aR activation. For in vivo
studies, two-kidney, one-clipped (2K1C) hypertensive rat model was established to
simulate renin-dependent hypertension conditions. C3a and C3aR expression was
detected in the clipped kidneys. SB290157 was injected intraperitoneally to block
C3a/C3aR signaling in 2K1C rats. Results: The results showed that renin
cleaved C3 into C3a and activated C3a/C3aR signaling in tubular epithelial cells
(TECs) from both humans and rats. In vitro results demonstrated that
C3a/C3aR activation impaired peroxisome proliferator-activated receptor alpha
(PPAR