Abstract: FR-PO220

Activation of PPAR-γ Suppresses AngII Induced Proliferation of HBZY-1 Cell via the GPCR/Gαq/PLCβ4/TRPC Signaling Pathway

Session Information

Category: Cell Biology

  • 202 Apoptosis, Proliferation, Autophagy, Cell Senescence, Cell Transformation

Authors

  • Wei, Linting, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
  • Fu, Rongguo, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
  • Lu, Jiamei, Second Affiliated Hospital of Xi''an Jiaotong University, Xi'an, China
Background

Mesangial cell proliferation and ECM is the main pathological change commonly can be seen in CKD. TRPC and PPAR-γ can regulate cell proliferation and apoptosis. AngII can induce mesangial cell proliferation and affect TRPC expressions. However, the mechanism has not been well elucidated. This study was aimed to investigate the role of TRPC and effect of rosiglitazone (RSG) in the proliferation of HBZY-1 cell and its underlying mechanisms.

Methods

Immuofluoresence staining and qRT-PCR were performed to examine the expressions of TRPCs in HBZY-1. Gene expressions of TRPC, PPAR-γ, RGS4, GPCR/Gαq/PLCβ4/TRPC signaling pathway and downstream main proliferative molecules (PCNA, SKP2, P21 and P27) were detected by qRT-PCR and Western blotting. Additionally, changes in intracellular Ca2+ concentration were determined through Fluo-4 Ca2+ imaging and cell cycle conditions were examined by flow cytometry.

Results

Our results found that TRPC1and TRPC6 were at higher expression levels in HBZY-1. Following AngII stimulation, there were increasing expressions of TRPC1 and TRPC6, Ca2+ influx, elevated gene expressions of PCNA and SKP2, decresing expressions of P21 and P27 and declined G0/G1 percentage (NC vs AngII, p<0.05). While silencing the TRPC1and TRPC6 by RNA interference led to decreasing in Ca2+ influx, G0/G1 cell cycle arrest and attenuated cell proliferations (p<0.05). Notably, activated PPAR-γ by RSG up-regulated RGS4 (regulators of G protein signaling) expressions, which can interact with the Gαq family to inhibit Gαq-mediated signaling pathways. The results were similar to silencing the TRPC1and TRPC6 by RNA interference techniques (p<0.05). All these results indicate that RSG could inhibite HBZY-1 cell proliferation via AT1R/Gαq/PLCβ4/TRPC signaling pathways.

Conclusion

This study suggests that activation of PPAR-γ and down-regulation of TRPC might be promising therapeutic targets for the treatment of mesangial cell prolifrative glomerulonephritis.

Funding

  • Government Support - Non-U.S.