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Temporal expressions of cyclins and cyclin dependent kinases during renal development and compensatory growth
1Department of Internal Medicine, Chonbuk National University Medical School, Chonju, Korea.
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.
Insights
Cyclin and cyclin-dependent kinase (CDK) levels decrease after birth in developing kidneys. Adult kidney compensatory growth does not alter these cell cycle regulators, suggesting cell cycle withdrawal postnatally.
Area of Science:
- Molecular Biology
- Developmental Biology
- Nephrology
Background:
- Cyclins and cyclin-dependent kinases (CDKs) regulate the eukaryotic cell cycle.
- Understanding their role in renal development and growth is crucial.
Purpose of the Study:
- To examine the temporal expression of cyclins and CDKs during renal development and compensatory growth.
- To investigate the role of cell cycle regulators in kidney adaptation.
Main Methods:
- Analysis of mRNA and protein levels of cyclins and CDKs during embryonic, postnatal, and adult stages.
- Assessment of compensatory renal growth using unilateral nephrectomy (Unx) and subtotal nephrectomy (Snx) models.
- Immunohistochemistry and Western blot analysis to detect protein expression and modifications.
Main Results:
- mRNA levels of cyclins were high during embryonic development, decreasing postnatally.
- Protein levels of cdc2, CDK2, and proliferating cell nuclear antigen (PCNA) decreased after birth.
- CDK4 protein levels remained high throughout renal development.
- Compensatory renal growth induced by Unx or Snx did not alter cyclin or CDK expression.
- Snx increased PCNA in remaining viable renal tissue, localized near ischemic areas.
- A novel 40 kDa protein reacting with cyclin D3 antibody was observed after Snx.
Conclusions:
- Marked reductions in mitotic cyclins correlate with renal cell cycle withdrawal after birth.
- Adult kidney compensatory growth does not involve changes in cyclin and CDK expression.