Pressure oscillation regulates human mesangial cell growth and collagen synthesis

Experimental renal disease models establish glomerular hypertension as a crucial determinant in glomerulosclerosis progression and demonstrate that glomerular capillary pressure reduction delays sclerosis development. An oscillating pressure (OP) chamber was constructed as an in vitro model to study human mesangial cells. Cell cultures were grown under atmospheric pressure (AP) and a controlled OP corresponding to intraglomerular capillary pressure. We show that OP significantly decreases mesangial cell proliferation within 24 hours and attenuates DNA synthesis throughout a 7-day period. To explore the effects of OP on cell metabolism, cell-associated and medium-secreted extracellular (CA and EC, respectively) collagen synthesis were measured by [3H]proline incorporation. In subconfluent cultures, total CA and EC collagen synthesis was unaffected by OP, while in confluent cultures total EC collagen [3H]proline incorporation was increased. To determine whether OP influenced mesangial cell growth induction, the effects of increasing glucose in the cell culture media were investigated. Our data show that the high glucose growth stimulatory effect on cell number and DNA synthesis was suppressed by OP. Under high glucose conditions, total CA collagen synthesis was increased in confluent cultures, whereas the EC collagen fraction remained unchanged. In these cultures, OP caused an additional increase in CA collagen synthesis. This study shows that mesangial cell growth and collagen synthesis are influenced by hyperbaric OP, supporting the hypothesis that glomerular capillary pressure plays a role in progressive glomerulosclerosis development.