Fig. 4.

Deletion of endogenous C1r reduces folic acid (FA)-induced acute kidney injury (AKI), tubular injury, and inflammation. A: plasma creatinine levels at day 2 after FA injection were reduced in C1r^−/− mice (red circles) compared with wild-type (WT) mice (black circles). n = 8 WT mice and 4 C1r^−/− mice for vehicle treatment; n = 8 WT mice and 6 C1r^−/− mice for FA treatment. *P < 0.05. B: real-time PCR analysis of whole kidney tissue showing increased expression of the tubular injury marker kidney injury molecule-1 (Kim-1) and loss of expression of Klotho in WT mice (black circles), whereas C1r^−/− mice (red circles) showed decreased expression of Kim-1 and no significant loss of Klotho 2 days after FA administration. Monocyte chemoattractant protein-1 (MCP-1) expression was also decreased in C1r^−/− mice (*P < 0.01). C: real-time PCR analysis of whole kidney tissue for complement genes C1r, C1s, and C3 showed the absence of C1r in vehicle- and FA-treated C1r^−/− mice (red circles) compared with WT mice (black circles). C1s and C3 expression was also significantly reduced both in vehicle- and FA-treated C1r^−/− mice. n = 3 WT mice and 3 C1r^−/− mice for vehicle treatment; n = 5–7 WT mice and 6 C1r^−/− mice for FA treatment (**P < 0.005). D: images for periodic acid-Schiff (PAS) stain showing reduced tubular injury in FA-treated C1r^−/− mice (original magnification: ×200).