E-cadherin and claudin-4 expression has circadian rhythm in adult rat kidney.

Background: Urinary sodium excretion varies during the day. It is unknown whether expression levels of cell-cell junctions in the kidney are dynamic and associated with urinary sodium excretion.

Methods: Adult Sprague Dawley rats were fed ad libitum or exclusively during the day, or kept under fasting condition. We measured expression levels of Per2, E-cadherin and claudin-4 as representative molecules of the peripheral circadian clock, adherens junctions and tight junctions, respectively. We also measured sodium concentration in urine. Effects of aldosterone on expression levels of Per2 and claudin-4 were also studied. To see proliferating cells in the kidney, rats were labeled with 5-bromo-2'-deoxyuridine.

Results: In rats fed ad libitum, Per2, E-cadherin and claudin-4 mRNA showed robust circadian oscillation: the correlation coefficients (R values) of the cosinor fitting curves with a 24-hour cycle were 0.928, 0.999 and 0.983, respectively. Oscillation phases of these molecules shifted in response to restricted feeding (R=0.922, R=0.815 and R=0.821, respectively). E-cadherin and claudin-4 proteins also oscillated circadianly under ad libitum feeding (R=0.851 and R=0.999, respectively), which shifted in response to the restricted feeding (R=0.811 and R=0.985, respectively). Urinary sodium excretion was low when protein levels of E-cadherin and claudin-4 were high. Aldosterone or cell division did not account for mRNA oscillation of claudin-4 or E-cadherin in the kidney.

Conclusions: Expression of E-cadherin and claudin-4 has a circadian rhythm. The dynamic change in protein levels of E-cadherin and claudin-4 seems to coincide with that in the level of sodium excretion.