Hyperosmolality suppresses but TGF beta 1 increases MMP9 in human peritoneal mesothelial cells
Hyperosmolality suppresses but TGF beta 1 increases MMP9 in human peritoneal mesothelial cells
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DOI：
10.1038/ki.1997.42
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发表时间：
1997-01-01
影响因子：
19.6
通讯作者：
Ronco, PM
中科院分区：
文献类型：
--
作者：
Rougier, JP;Moullier, P;Ronco, PM
腹膜间皮细胞直接暴露在高渗透析液中，可能会增加细胞外基质的积聚，从而影响超滤。由于这些细胞位于含有IV型胶原的基底膜上，我们研究了培养的人腹膜间皮细胞产生IV型胶原酶的模式以及高渗和转化生长因子β1对它们的调节。从逆转录病毒转导SV40大T抗原的原代培养中获得了一株具有正常腹膜间皮细胞主要特征的细胞系(HMRSV5)。凝胶成像和Western印迹分析表明：(I)人腹膜间皮细胞产生和分泌MMP2和MMP9及其抑制物TIMP1和TIMP2；(Ii)高渗显著降低MMP9的表达，而不考虑时间和浓度依赖的渗透介质；(Iii)转化生长因子β1意外地增加指数生长细胞中MMP9的活性和蛋白，并能恢复融合培养中被高渗抑制的MMP9活性。为了排除SV40 Large-T抗原对基质金属蛋白酶的产生和调节的特定影响，这些结果在来自不同供体的内脏腹膜样本的原代培养中得到证实。因此，透析液的高渗透压可能有利于IV型胶原的积聚和腹膜基底膜的增厚，而感染过程中释放的转化生长因子β1可能导致IV型胶原的降解和间质胶原的替代。
Peritoneal mesothelial cells are directly exposed to hyperosmolar dialysates which may enhance extracellular matrix accumulation and hence compromise ultrafiltration. Because these cells are laid on a type IV collagen containing basement membrane, we examined the pattern of type IV collagenases produced by cultured human mesothelial cells and their regulation by hyperosmolality and TGF beta 1. A cell line (HMrSV5) exhibiting major features of normal peritoneal mesothelial cells was derived from a primary culture retrovirally transduced with SV40 large-T antigen. Zymography and Western blot analysis showed that: (i) human peritoneal mesothelial cells produced and excreted MMP2 and MMP9 and their inhibitors TIMP1 and TIMP2; (ii) hyperosmolality drastically reduced the expression of MMP9 irrespective of the osmolyte used in a time- and concentration-dependent manner; (iii) TGF beta 1 unexpectedly increased MMP9 activity and protein in exponentially growing cells and could restore MMP9 activity suppressed by hyperosmolality in confluent cultures. To exclude a specific effect of SV40 large-T antigen on matrix metalloproteinases production and regulation, these results were confirmed in primary cultures derived from visceral peritoneal samples from different donors. Therefore, the hyperosmolality of dialysates may favor an accumulation of type IV collagen and thickening of peritoneal basement membrane, while TGF beta 1 released during infections may induce the degradation of type IV collagen and its replacement by interstitial collagens.