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Abstract: SA-PO748

Podocyte Autophagy and Cell Survival Is Regulated by the Circadian Clock Gene

Session Information

Category: Glomerular Diseases

  • 1304 Glomerular Diseases: Podocyte Biology


  • Wang, Lulu, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
  • Jiang, Lei, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
  • Yang, Junwei, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China

The circadian clock is a ubiquitous system in mammals which synchronizes cellular, tissue, and systemic biological functions with 24-hour environmental cycles. CLOCK (Circadian locomoter output Cycles protein kaput) is a core component of the molecular clocks. It contains a BHLH-PAS domain and forms a heterodimer with BMAL1 (Brain and Muscle Arnt-like 1), acting in the positive branch of the circadian transcription/translation feedback loop. Previous study had identified that the intrinsic circadian clock BMAL1 in podocytes controls glomerular filtration rate. Little is known about the Clock and podocytes. The study aimed to explore the effects of Clock on podocytes.


In vitro, the primary podocyte was used to elaborate the role of Clock on podocytes by knockdown of Clock by siRNA. Chromatin immunoprecipitation (CHIP) sequence was employed to detect association between Clock and autophagy. In vivo, we made mouse sleep fragmentation to constructed circadian rhythm disorder model. The podocyte specific Clock knockout mice (podocyte-Clock-/-) were also constructed.


Loss of Clock caused podocyte death. There was an increased urinary albumin excretion and podocytes injury in Podocyte-Clock-/- mice compared to control mice. We also found that sleep fragmentation led to the loss of circadian clock oscillation, the fusion of foot processes and albuminuria. CHIP-seq and qPCR analysis confirmed that Clock bonded to the promoter of Becn1 and Atg12. Circadian rhythms disorder impaired autophagy, which promoted podocyte death.


Our study revealed the critical role of Clock circadian rhythm in podocyte. Mechanistically, Clock dependent circadian autophagy is indispensable for podocyte to adapt stress response or nutrient metabolism.


  • Government Support – Non-U.S.