Applied pressure modulates mesangial cell proliferation and matrix synthesis.
Substantial in vivo evidence suggests a significant role for glomerular capillary pressure in the pathogenesis of progressive glomerulosclerosis. One presently available in vitro system allows one to study cells while undergoing stretch. However, no comparable system is available to allow one to study in an in vitro system how direct application of pressure to glomerular mesangial cells might result in the development of glomerulosclerosis. We constructed a pressure chamber in which mesangial cells could be subjected to an applied pressure by means of a roller pump and adjustable outlet valve. Mesangial cells were grown either under control conditions or under an applied pressure of 40 to 50 mm Hg corresponding to physiologic intraglomerular pressure. Application of pressure significantly decreased mesangial cell number in prolonged culture though no discernable effect on cell proliferation could be detected after only short-term exposure. Long-term exposure to increased pressure significantly enhanced mesangial cell [3H] proline incorporation, a marker for synthesis of the matrix component collagen, an event considered to be a precursor to the development of glomerulosclerosis. Mesangial cell matrix synthesis was significantly greater for cells subjected to 50 to 60 mm Hg pressure compared to 40 to 50 mm Hg pressure. Secretory products from macrophages subjected to 40 to 50 mm Hg of applied pressure were found to significantly enhance mesangial cell proliferation compared to secretory products from macrophages grown under normal pressure. The enhancement of mesangial cell matrix synthesis by pressure could not be attributed to any change in partial pressure of oxygen in the media nor pH. These data suggest that the direct application of pressure to mesangial cells may result in the development of glomerulosclerosis by increasing mesangial cell matrix synthesis. These in vitro data support a role for glomerular capillary pressure in the pathogenesis of progressive glomerulosclerosis.
Mattana
J
J
Department of Medicine, Long Island Jewish Medical Center, New Hyde Park, New York 11042, USA.
Singhal
P C
PC
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods*; D002455:Cell Division; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000166:cytology*; D008365:Manometry; D011312:Pressure; D051381:Rats