Related Experiment Video

Updated: Aug 15, 2026

Optimizing Isolation and Purification of Murine Glomerular Mesangial Cells
04:46

Optimizing Isolation and Purification of Murine Glomerular Mesangial Cells

Published on: March 7, 2025

The cyclin-dependent kinase inhibitor p21 limits murine mesangial proliferative glomerulonephritis

Toshiaki Monkawa1, Jeffrey Pippin, Yoshikage Yo

  • 1Division of Nephrology, University of Washington, Seattle, Washington, USA.

Nephron. Experimental Nephrology
|September 24, 2005
PubMed
Abstract

Insights

The cyclin-dependent kinase inhibitor p21 regulates mesangial cell proliferation in glomerulonephritis but does not affect apoptosis, leading to delayed healing in deficient mice.

Area of Science:

  • Nephrology
  • Immunology
  • Cell Biology

Background:

  • Mesangial cell (MC) proliferation and apoptosis are key to glomerulonephritis (GN) progression and resolution.
  • Cyclin-dependent kinase (CDK) inhibitors, like p21, regulate cell cycle proteins involved in proliferation and apoptosis.
  • The specific role of p21 in acute mesangial proliferative GN remains unclear.

Purpose of the Study:

  • To investigate the role of p21 in regulating MC proliferation and apoptosis during anti-MC serum-induced GN.
  • To test the hypothesis that p21 controls MC proliferation and apoptosis in this GN model.

Main Methods:

  • Wild-type (p21+/+) and p21-deficient (p21-/-) mice were subjected to anti-MC serum induction.
  • Renal function, histology, DNA synthesis (BrdU, Ki-67), and apoptosis (TUNEL) were assessed at days 6 and 12.

Main Results:

  • p21 deficiency worsened renal function and exacerbated MC proliferative GN features, including necrosis and hypercellularity.
  • Mesangial cell DNA synthesis was increased in p21-/- mice, while apoptosis remained unchanged.
  • p21-/- mice exhibited severe glomerular and tubulointerstitial fibrosis.

Conclusions:

  • The CDK-inhibitor p21 is a key regulator of the mesangial cell proliferative response to immune-mediated kidney injury.
  • p21 does not influence the apoptotic response, contributing to delayed resolution of GN in its absence.
  • These findings highlight p21's critical role in managing the proliferative aspect of glomerulonephritis.

More Related Videos

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...