Eur Rev Med Pharmacol Sci 2017; 21 (16): 3634-3641

The role of PTEN up-regulation in suppressing glomerular mesangial cells proliferation and nephritis pathogenesis

H.-Y. Gao, C.-X. Han

The Kidney Internal Medicine of Xianyang First People’s Hospital, Xianyang, Shaanxi, China. heyangao91@163.com


OBJECTIVE: Over-proliferation of mesangial cells is the major pathological change of mesangial proliferative glomerulonephritis (MPGN). PTEN-PI3K/AKT pathway plays a role in regulating proliferation of mesangial cells. Anti-thymocyte serum nephritis (ATSN) is a widely used animal model for studying MPGN. This study established ATSN model, on which the role of PTEN-PI3K/AKT signal pathway in MPGN pathogenesis was investigated.

MATERIALS AND METHODS: ASTN rat model was established in parallel with control group. Protein expressions of PTEN, p-AKT, PCNA, Cyclin D1 and Bcl-2 were quantified, along with glomerular mesangial cell (GMC) counting. Rat mesangial cell (RMC) was treated with 0 or 10 ng/mL IL-6, followed by flow cytometry analysis for apoptosis, cycle and PCNA expression. Expressions of PTEN, p-AKT, PCNA, Cyclin D1 and Bcl-2 were measured. RMC was treated with pSicoR-PTEN and/or LY294002, followed by the treatment of 10 ng/mL IL-6 for 48 h. Cell apoptosis, cycle, PCNA expression and protein expression were measured.

RESULTS: Lower PTEN expression was found in renal cortex of ATSN rats, along with increasing levels of p-AKT, PCNA, Cyclin D1, Bcl-2, and higher GMCs, compared to that in control rats. IL-6 treatment increased protein expression in RMC, facilitated cell proliferation and cycle progression and suppressed apoptosis. Over-expression of PTEN and/or LY294002 remarkably decreased protein expression in RMC, inhibited the effect of IL-6 on proliferation, and induced cell apoptosis and cycle arrest.

CONCLUSIONS: The down-regulation of PTEN played a role in enhancing PI3K/AKT pathway activity, facilitating GMC proliferation and MPGN pathogenesis.

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To cite this article

H.-Y. Gao, C.-X. Han
The role of PTEN up-regulation in suppressing glomerular mesangial cells proliferation and nephritis pathogenesis

Eur Rev Med Pharmacol Sci
Year: 2017
Vol. 21 - N. 16
Pages: 3634-3641