Age-related TFEB downregulation in proximal tubules causes systemic metabolic disorders and occasional apolipoprotein A4-related amyloidosis.

ABSTRACT: With the aging of society, the incidence of chronic kidney disease (CKD), a common cause of death, has been increasing. Transcription factor EB (TFEB), the master transcriptional regulator of the autophagy/lysosomal pathway, is regarded as a promising candidate for preventing various age-related diseases. However, whether TFEB in the proximal tubules plays a significant role in elderly patients with CKD remains unknown. First, we found that nuclear TFEB localization in proximal tubular epithelial cells (PTECs) declined with age in both mice and humans. Next, we generated PTEC-specific Tfeb-deficient mice and bred them for up to 24 months. We found that TFEB deficiency in the proximal tubules caused metabolic disorders and occasionally led to apolipoprotein A4 (APOA4) amyloidosis. Supportin

SUBMITTER: Nakamura J 

PROVIDER: S-EPMC11948592 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature