APPLIED PRESSURE MODULATES MESANGIAL CELL-PROLIFERATION AND MATRIX SYNTHESIS
APPLIED PRESSURE MODULATES MESANGIAL CELL-PROLIFERATION AND MATRIX SYNTHESIS
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DOI：
10.1016/0895-7061(95)00233-f
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发表时间：
1995-11-01
影响因子：
3.2
通讯作者：
SINGHAL, PC
中科院分区：
文献类型：
--
作者：
MATTANA, J;SINGHAL, PC
大量的体内证据表明肾小球毛细血管压力在进行性肾小球硬化的发病机制中起重要作用。一种目前可用的体外系统允许人们在进行拉伸时研究细胞。然而，没有可比较的系统允许人们在体外系统中研究直接对肾小球系膜细胞施加压力如何导致肾小球硬化的发展。我们构建了一个压力室，在这个压力室中，系膜细胞可以通过滚轴泵和可调节的出口值来承受施加的压力。系膜细胞在控制条件下生长，或在与生理肾小球内压力相对应的40至50毫米汞柱的施加压力下生长。在长时间的培养中，施加压力显著减少了系膜细胞的数量，但在短期暴露后对细胞增殖没有明显的影响。长期暴露于增高的压力下，可显著增强系膜细胞[H-3]脯氨酸的掺入，这是基质成分胶原合成的标志，被认为是肾小球硬化的前兆。与承受40至50毫米汞柱压力的细胞相比，承受50至60毫米汞柱压力的细胞的系膜细胞基质合成显著增加。与正常压力下生长的巨噬细胞的分泌产物相比，巨噬细胞在施加40至50毫米汞柱压力下的分泌产物显著增强了系膜细胞的增殖。压力对系膜细胞基质合成的增强不能归因于介质中氧分压或ph的任何变化。这些数据表明，直接对系膜细胞施加压力可能通过增加系膜细胞基质合成而导致肾小球硬化的发生。这些体外数据支持肾小球毛细血管压力在进行性肾小球硬化发病机制中的作用。
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 value. 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 [H-3]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.