Reciprocal regulation between the molecular clock and kidney injury

Area of Science:

• Nephrology
• Molecular Biology
• Chronobiology

Background:

• Tubulointerstitial fibrosis is a key factor in chronic kidney disease.
• The role of the molecular clock in kidney fibrosis is not fully understood.

Purpose of the Study:

• To investigate the relationship between the molecular clock and kidney damage/fibrosis.
• To explore the impact of clock gene deficiencies on renal injury models.

Main Methods:

• Used mouse models of kidney injury (unilateral ureteral obstruction, folic acid, adenine nephrotoxicity).
• Utilized genetically modified mice lacking Bmal1, Clock, Cry1, and Cry2 clock components.
• Examined human tubular epithelial cells treated with TGFβ.

Main Results:

• The molecular clock pathway was enriched in damaged kidney cells with metabolic alterations.
• TGFβ altered clock component expression in human tubular epithelial cells.
• Absence of Cry1 and Cry2 exacerbated fibrosis by promoting neutrophil recruitment and altering metabolism-related gene expression.

Conclusions:

• Renal damage disrupts the kidney's peripheral molecular clock.
• Disrupted molecular clock promotes metabolic derangement, inflammation, and fibrosis.