Acute renal tubular necrosis is a well-known pathological change in acute kidney injury (AKI). The death of tubular cells stimulates the proliferation of neighboring survived tubular cells to recover total tubular function. However, recent studies revealed that AKI concomitant with sepsis does not show characteristic tubular cell death. It has not been examined whether septic AKI accelerates cell proliferation or not. In the present study, we examined the time-course changes in tubular cell proliferation after induction of sepsis by either lipopolysaccharide or cecum ligation and puncture.Design and method:
The cell cycle transition was analyzed by immunohistochemistry for Ki67 and tyrosine analogue and by using Fucci mice that express Kusabira Orange at G1 phase of cell cycle.Results:
Fucci mice (8 weeks old) showed decrease in the numbers of G1-phase cell in the ultra-early phase (-2h) of sepsis. The rapid cell cycle transition was confirmed by Ki67 or tyrosine analogue staining only in young mice (-12 weeks), not in old mice (8–14 months). Etoposide, an anti-cancer drug, abolished the increase in proliferation in young mice. Importantly, old mice or etoposide-treated young mice showed severer AKI than young mice did.Conclusions:
These results indicate the tubular cell proliferation without significant cell death in sepsis, possibly as a compensatory mechanism against the development of AKI. The cell senescence might disrupt this mechanism and increase the AKI risk.