Trifluoperazine Inhibits Mesangial Cell Proliferation by Arresting Cell Cycle-Dependent Mechanisms

Baodong Wang1, Xiaoshuang Zhou1, Yanqin Wang1

  • 1Department of Nephrology, Affiliated People's Hospital of Shanxi Medical University, Shanxi Provincial People's Hospital, Shanxi Kidney Disease Institute, Taiyuan, Shanxi, China (mainland).

Insights

Trifluoperazine (TFP) inhibits renal mesangial cell proliferation by arresting the cell cycle. This drug shows potential for treating mesangial proliferative diseases by affecting key signaling pathways.

Area of Science:

  • Nephrology
  • Cell Biology
  • Pharmacology

Background:

  • Trifluoperazine (TFP) is known to inhibit cancer cell proliferation.
  • Its effects on renal proliferative diseases remain largely uncharacterized.
  • This study investigates TFP's impact on human renal mesangial cell proliferation.

Purpose of the Study:

  • To examine the effects of TFP on human renal mesangial cell proliferation.
  • To elucidate the underlying molecular mechanisms of TFP's action.
  • To evaluate TFP's therapeutic potential in lupus nephritis models.

Main Methods:

  • In vivo and in vitro cell proliferation assays (HE staining, PCNA, Ki-67, MTT assay).
  • Cell cycle analysis using flow cytometry.
  • Western blot analysis for cell cycle proteins (cyclin D1, CDK2, CDK4, p21) and signaling pathways (MAPK, PI3K/AKT).

Main Results:

  • TFP inhibited mesangial cell proliferation dose- and time-dependently in vitro and in vivo.
  • TFP induced G0/G1 cell cycle arrest by altering cyclin and CDK expression.
  • TFP suppressed PI3K/AKT and JNK/MAPK signaling pathways and reduced serum creatinine in lupus mice.

Conclusions:

  • TFP exhibits inhibitory effects on mesangial cells through G1 cell cycle arrest.
  • Inactivation of PI3K/AKT and JNK/MAPK pathways mediates TFP's action.
  • TFP demonstrates potential as a therapeutic agent for mesangial proliferative diseases.

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