Statistical comparisons were performed with two-tailed unpaired t test or analysis of variance (ANOVA) followed by post hoc Bonferroni test using SPSS (IBM) software, and each series of experiments was repeated at least three times. P values <0.05 were considered statistically significant. For all figures and supplementary figures, quantitative data are presented as means ± SD. *P < 0.05; **P < 0.01; ***P < 0.001; NS, not significant by two-tailed unpaired t test unless specified otherwise. Adequate sample sizes of experiments were estimated on the basis of our pilot experiments and experience with similar measurements to ensure adequate power to detect a specified effect size. For animal analyses, at least three animals were assigned to each experimental group according to standard scientific conventions. We tried to reach a conclusion for each individual experiment, using as small a size of samples as possible. No data were excluded, whereas the investigators were not blinded to any group allocations, which were randomly performed for in vivo or in vitro experiments.