Fig. 1: MLKL mediates septic and ischemic injury.
a Survival after injection of recombinant human TNFα into wt, RIPK3-ko or MLKL-ko mice. b−c siRNA-mediated knockdown of RIPK3 or MLKL protects murine renal tubular cells (MCT) from TNFα/TWEAK/IFNγ(TTI) + zVAD-fmk (zVAD)-induced necroptosis 24 h after induction of cell death. Western blots for RIPK3 and MLKL indicate the efficiency of the siRNA-mediated knockdown. d−g Head-to-head comparison of RIPK3-deficient mice to MLKL-deficient mice in the model of renal ischemia-reperfusion injury (IRI). Eight-week-old RIPK3-ko and MLKL-ko mice were subjected to 30 min of renal pedicle clamping before the onset of reperfusion. Histological changes (d, scale bars = 50 µm) were quantified (e) 48 h later by employing a renal tubular damage score (TDS, see Methods for details), and functional markers of acute kidney injury (serum urea (f) and serum creatinine (g)) were measured. No statistically significant differences were detected between RIPK3-ko and MLKL-ko mice in any of these models. Statistical significance was indicated: n.s.: not statistically significant, p < 0.05 (*), p < 0.01 (**), p < 0.001 (***), n = 10−17 per group
