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Updated: Feb 26, 2026

Optimizing Isolation and Purification of Murine Glomerular Mesangial Cells
Published on: March 7, 2025
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).
Abstract:
BACKGROUND It has been reported that trifluoperazine (TFP) inhibits proliferation of cancer cells, however, the effects of TFP in renal proliferation diseases are still unclear. This study examined the effects of TFP on proliferation of human renal mesangial cells and analyzed the underlying mechanisms. MATERIAL AND METHODS Cell proliferation in vivo was determined by HE staining, immunohistochemistry of proliferating cell nuclear antigen (PCNA), and Western blot analysis (Ki-67 and PCNA). Effects of different TFP concentrations and treatment duration on cell proliferation and cell cycle were analyzed using the MTT assay and flow cytometry. Expression of G0/G1 phase cell cycle-related proteins and TFP-induced MAPK and PI3K/AKT signaling pathways was estimated with Western blot analysis. RESULTS Our findings suggest that TFP inhibits cell proliferation in a dose- and time-dependent manner and decreased PCNA and Ki-67 levels in lupus MRL/lpr mice. TFP arrested the cell cycle in the G0/G1 phase, down-regulating cyclin D1, CDK2, and CDK4, and up-regulating p21 expression in a dose-dependent manner. In addition, TFP inhibited p-AKT and p-JNK, possibly by suppressing the activation of PI3K/AKT and JNK/MAPK signaling pathways. TFP treatment remarkably reduced the levels of serum creatinine (Cr) in lupus mice. CONCLUSIONS TFP exhibits inhibitory activity against mesangial cells in vivo and in vitro, which is associated with G1 cell cycle arrest by inactivation of PI3K/AKT and JNK/MAPK signaling pathways. These results suggest the potential of TFP in treatment of mesangial proliferative diseases.
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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