Effects of polycystin‑1 N‑terminal fragment fusion protein on the proliferation and apoptosis of rat mesangial cells

Guan,Tianjun; Gao,Qing; Chen,Ping; Fu,Lili; Zhao,Haidan; Zou,Zhuying; Mei,Changlin

doi:10.3892/mmr.2014.2354

Effects of polycystin‑1 N‑terminal fragment fusion protein on the proliferation and apoptosis of rat mesangial cells

Authors:
- Tianjun Guan
- Qing Gao
- Ping Chen
- Lili Fu
- Haidan Zhao
- Zhuying Zou
- Changlin Mei
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Affiliations: Department of Nephrology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, P.R. China, Division of Nephrology, Center of Kidney Disease, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China, Department of Nephrology, Navy General Hospital, Beijing 100000, P.R. China
Published online on: June 26, 2014 https://doi.org/10.3892/mmr.2014.2354
Pages: 1626-1634

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Abstract

Mesangial proliferative glomerulonephritis (MsPGN) is characterized by widespread mesangial cell proliferation and an accumulation of extracellular matrix (ECM) in the mesangial area. In a previous study we developed a polycystin‑1 N‑terminal fragment (PC‑1 NF) fusion protein that inhibits the proliferation of cyst‑lining epithelial cells in autosomal dominant polycystic kidney disease. In addition, the PC‑1 NF fusion protein arrests the cell cycle of cancer cells at the G0/G1 phase, inhibiting their proliferation. In the present study, the effect of the PC‑1 NF fusion protein on MsPGN was investigated. It was found that the PC‑1 NF fusion protein inhibited the proliferation of rat mesangial cells and induced G0/G1 phase arrest and apoptosis in vitro. PC‑1 NF fusion protein treatment also resulted in a decrease in mRNA expression levels of proliferating cell nuclear antigen, cyclin D1 and B‑cell lymphoma‑2 (Bcl‑2) and an increase in mRNA expression levels of Bcl‑2‑associated X protein (Bax) and p21Waf1. Furthermore, a decrease in Bcl‑2, c‑fos, c‑jun and protein kinase C‑α protein levels was observed, whereas Bax protein levels increased. Additionally, PC‑1 NF fusion protein induced ECM degradation and inhibited ECM expansion. The results also demonstrated that PC‑1 NF fusion protein treatment resulted in a decrease in type IV collagen and tissue inhibitor of metalloproteinase mRNA levels but an increase in matrix metalloproteinase 2 mRNA levels. In combination, these results suggest that the PC‑1 NF fusion protein inhibits proliferation, promotes apoptosis and induces ECM degradation in MsPGN rats. This study offers novel perspectives for the treatment of MsPGN.

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