Brain and muscle Arnt-like protein 1 (BMAL1) is a transcription factor that forms heterodimers with circadian locomotor output cycles kaput (CLOCK) and drives transcription from E-box elements, thereby regulating the circadian rhythms of gene expression. The kidney expresses numerous rhythmic genes and exhibits circadian physiological function regulation. Circadian rhythm abnormalities, such as sleep disorders and excessive daytime sleepiness, are particularly frequent in patients with chronic kidney disease (CKD). Furthermore, reduced amplitude and phase disruption in clock gene expression rhythms have been reported in mouse CKD models. These results suggest that circadian disruption is associated with renal pathophysiology. However, the role of BMAL1 in the repair process following acute kidney injury (AKI) remains unclear; therefore, this study aimed to elucidate its role in kidney repair following ischemia–reperfusion injury (IRI). We found that the tamoxifen (TAM)-inducible global Bmal1 knockout (BKO) mouse kidneys exhibited increased lipid accumulation, enhanced fibrosis, and delayed kidney repair post-IRI, and that these abnormalities were associated with reduced Peroxisome proliferator-activated receptor alpha (Pparα) expression. Furthermore, treatment with a PPARα agonist reduced these abnormalities in BKO mice. Collectively, our findings demonstrate that the BMAL1–PPARα axis promotes post-AKI kidney repair.
Kitaura et al. (Sat,) studied this question.