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Updated: Apr 19, 2026
Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
Published on: June 6, 2017
Cell cycle control in the kidney
Dana Thomasova1, Hans-Joachim Anders1
1Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität, Munich, Germany.
Abstract:
Proper control of the cell cycle is mandatory during homeostasis and disease. The balance of p53 and MDM2 integrates numerous signalling pathways to regulate the cell cycle, which is executed by multiple proteins including the cyclins, cyclin kinases and cyclin kinase inhibitors. Mutations or environmental factors that affect cell cycle control can lead to inappropriate hyperplasia or cancer as well as to cell loss and tissue atrophy. Normal kidney function is maintained largely by post-mitotic quiescent cells in the G0 phase with a low turnover. Early cell cycle activation during kidney injury contributes to cell death via mitotic catastrophe, i.e. death via mitosis, e.g. of cell with significant DNA damage. At later stages, cell cycle entry supports tissue regeneration and functional reconstitution via cell hypertrophy and/or cell proliferation. It is of note that so-called proliferation markers such as Ki67, PCNA or BrdU identify only cell cycle entry without telling whether this results in cell hypertrophy, cell division or mitotic catastrophe. With this in mind, some established concepts on kidney injury and regeneration are to be re-evaluated. Here, we discuss the components and functional roles of p53/MDM2-mediated cell cycle regulation in kidney homeostasis and disease.
Insights
Cell cycle regulation by p53 and MDM2 is crucial for kidney homeostasis and disease. Understanding this balance is key to re-evaluating kidney injury and regeneration concepts.
Area of Science:
- Cell Biology
- Renal Medicine
- Molecular Biology
Background:
- Proper cell cycle control is essential for maintaining tissue homeostasis and preventing disease.
- The p53 and MDM2 complex integrates signaling pathways to regulate the cell cycle, involving cyclins, cyclin kinases, and inhibitors.
- Dysregulation of cell cycle control can lead to hyperplasia, cancer, cell loss, or tissue atrophy.
Purpose of the Study:
- To discuss the components and functional roles of p53/MDM2-mediated cell cycle regulation in kidney homeostasis and disease.
- To re-evaluate established concepts of kidney injury and regeneration in light of cell cycle dynamics.
- To highlight the limitations of proliferation markers in distinguishing cellular outcomes post-cell cycle entry.
Main Methods:
- Literature review and conceptual analysis of p53/MDM2-mediated cell cycle regulation.
- Discussion of the role of cell cycle regulators in kidney homeostasis and response to injury.
- Analysis of the implications of early vs. late cell cycle activation in kidney injury and regeneration.
Main Results:
- Kidney homeostasis relies on quiescent cells, with early cell cycle activation during injury potentially leading to mitotic catastrophe.
- Later cell cycle entry supports kidney regeneration through hypertrophy and proliferation.
- Standard proliferation markers (Ki67, PCNA, BrdU) indicate cell cycle entry but not the ultimate cellular fate (hypertrophy, division, or catastrophe).
Conclusions:
- The p53/MDM2 pathway plays a critical role in balancing cell cycle control for kidney health and disease.
- Re-evaluation of kidney injury and regeneration paradigms is necessary, considering the nuanced outcomes of cell cycle activation.
- A deeper understanding of cell cycle regulation is vital for developing effective therapeutic strategies for kidney diseases.
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