Effects Of High Hydrostatic Pressure On Rat Mesangial Cell

Objective: Persistent static pressure increases the proliferation of rat mesangial cell ( RMC) and the accumulation of extracellular matrix (ECM). A periodically fluctuat-ing pressure (PFP) chamber was constructed as an in vitro model to explore the effects of PFP on RMC and to determine whether Ang II and transforming growth factor-β1(TGF-β1) were involved regulated. Methods: Cultured RMC of 3-6th passage were exposed to atmosphere (0mmHg, AH), low pressure (30mmHg, LP), moderate pressure (60mmHg, MP) and high pressure (100 mmHg, HP) for 6, 12, 24, 48h respectively. There are three groups in each pressure condition. One as control, the other two were interfered with captopril (10 μmol/L), or irbesartan (10μmol/L). Cell proliferation was quantified by using MTT method, whose OD value reflected cell proliferation. Concentration of Ang II in conditioned medium was measured by radioimmunoassay. The content of TGF-β1, collage I(α),collage IV(α) were investigated by western blot in conditioned medium. Results: Compared with AH, cell proliferation and function of RMC cultured under LP was uninfluenced. OD value in MP, HP groups were significantly increased at 6h (0.59±0.09, 0.63±0.11 vs 0.42±0.07 P＜0.05), persistently increased in time-dependent manner during the range in our study, which attained the highest level at 48h(1.25±0.20, 1.54±0.36 vs 0.74±0.13 P＜0.05). The change of Ang II was similar in cell proliferation. Compared with AH, the concentration of collage I(α) was increased in MP, HP at 6h (1.76±0.38, 2.11±0.55 vs 1.00 P＜0.05), was higher at 48h (2.46±0.48, 2.76±0.64 vs 1.41±0.34 P＜0.05). The level of TGF-β1 was increased in MP,HP at 6h (2.17±0.26, 2.62±0.51 vs 1.00 P＜0.05)and at 48h (3.05±0.48, 3.97±0.66vs 1.74±0.42 P＜0.05). The degree of increase in collage IV(α) was similar in TGF-β1. Irbesartan and captopril suppressed the proliferation of RMC and decreased the level of TGF-β1, collage I(α), collage IV(α) in MP and HP, but no influence in AH. The concentration of Ang II was not changed by irbesartan, but obviously reduced by captopril in MP and HP. Irbesartan and captopril had no effect on the level of Ang II in AH and LP. Conclusion: High hydrostatic pressure induces RMC proliferation, accumulation of ECM. The mechanism is involved with increased of the level of Ang II and TGF-β1 induced by high hydrostatic pressure.