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 demonstra te that glomerular capillary pressure reduction delays sclerosis devel opment. An oscillating pressure (OP) chamber was constructed as an in vitro model to study human mesangial cells. Cell cultures were grown u nder atmospheric pressure (AP) and a controlled OP corresponding to in traglomerular capillary pressure. We show that OP significantly decrea ses mesangial cell proliferation within 24 hours and attenuates DNA sy nthesis throughout a 7-day period. To explore the effects of OP on cel l metabolism, cell-associated and medium-secreted extracellular (CA an d EC, respectively) collagen synthesis were measured by [H-3]proline i ncorporation. In subconfluent cultures, total CA and EC collagen synth esis was unaffected by OP, while in confluent cultures total EC collag en [H-3]proline incorporation was increased. To determine whether OP i nfluenced mesangial cell growth induction, the effects of increasing g lucose in the cell culture media were investigated. Our data show that the high glucose growth stimulatory effect on cell number and DNA syn thesis was suppressed by OP. Under high glucose conditions, total CA c ollagen 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 me sangial cell growth and collagen synthesis are influenced by hyperbari c OP, supporting the hypothesis that glomerular capillary pressure pla ys a role in progressive glomerulosclerosis development.