Temporal expressions of cyclins and cyclin dependent kinases during renal development and compensatory growth

Abstract

The family of cyclins and cyclin-dependent kinases (CDKs) are important participants in the regulation of eukaryotic cell cycle. Our purpose was to examine temporal expressions of cyclins and CDKs during renal development and compensatory growth. During embryonic development the mRNA levels of all cyclins were high, and after birth their levels decreased at different rates. G2 and M phase cyclins, cyclin A and B, decreased immediately after birth. G1 and S phase cyclins, cyclins D1, D2, D3, and E, were observed during all stages of development and maintained almost constant levels until seven days after birth. They decreased thereafter and expressed very low levels during the adult period. The protein levels of cdc2, CDK2, and proliferating cell nuclear antigen (PCNA) were high during embryonic renal development and slowly decreased after birth. Their levels were very low during the youth and adult periods. Levels of CDK4 protein were high and did not change during renal development. Compensatory hypertrophic renal growth (CHRG) induced by unilateral nephrectomy (Unx) did not increase any cyclins, CDKs or PCNA. Subtotal nephrectomy (Snx) did not increase any cyclins or CDKs in remaining viable renal tissue (RVRT). However, Snx increased PCNA in RVRT. An immunohistochemical study revealed that PCNA was induced in a limited area adjacent to ischemic areas. Interestingly, Western blot analysis of protein extracts from RVRT showed the induction of a new 40 kDa protein that cross-reacted with the cyclin D3 antibody. These findings suggest that the marked reductions in mitotic cyclins may be associated with the withdrawal of renal cell cycle after birth. In addition, expressions of cyclins and CDKs did not change in the adult kidney during active phase of compensatory hypertrophic growth.