Acquired resistance to rechallenge injury after acute kidney injury in rats is associated with cell cycle arrest in proximal tubule cells.

Acquired resistance to rechallenge injury after acute kidney injury in rats is associated with cell cycle arrest in proximal tubule cells. Am J Physiol Renal Physiol. 2016 Jan 28;:ajprenal.00380.2015 Authors: Iwakura T, Fujigaki Y, Fujikura T, Ohashi N, Kato A, Yasuda H Abstract Rats that have recovered from severe proximal tubule (PT) injury induced by uranyl acetate (UA), a toxic stimulus, developed resistance to subsequent UA treatment. We investigated cell cycle status and progression in PT cells in relation to this acquired resistance. Fourteen days after pretreatment with saline (vehicle group) or UA [acute kidney injury (AKI) group], rats were injected with UA or lead acetate (a proliferative stimulus). Cell cycle status (G0/G1/S/G2/M) was analyzed by flow cytometry. The expression of cell cycle markers, cyclin-dependent kinase inhibitors, and phenotypic markers were examined by immunohistochemistry. Cell cycle status in PT cells in the AKI group was comparable to those of the vehicle group. However, more early-G1 phase cells (cyclin D1- or Ki67-) and p21+ or p27+ cells were found in the PT of the AKI group than in that of the vehicle group. UA induced G1 arrest and inhibited S phase progression with earlier dedifferentiation and less apoptosis in PT cells of the AKI group. Lead acetate induced proliferation without dedifferentiation but with delayed G0-G1 transition and inhibited S phase progression in PT cells in the AKI gro...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research