SPARC regulates TGF-beta 1-dependent signaling in primary glomerular mesangial cells
SPARC regulates TGF-beta 1-dependent signaling in primary glomerular mesangial cells
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DOI：
10.1002/jcb.20008
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发表时间：
2004-04-01
影响因子：
4
通讯作者：
Sage, EH
中科院分区：
文献类型：
--
作者：
Francki, A;McClure, TD;Sage, EH
富含半胱氨酸的酸性分泌蛋白(SPARC)是基质细胞蛋白家族的一员，调节细胞与细胞外基质(ECM)的多效性因子和蛋白的相互作用。虽然已经认识到转化生长因子-β1(TGF-β1)诱导了SPARC和I型胶原的表达，但我们最近发现，SPARC通过依赖于转化生长因子-β1的途径调节肾小球系膜细胞中转化生长因子-β1和I型胶原的表达，并在SPARC和转化生长因子-β1之间提出了一个相互的、自分泌的调节反馈环。在此，我们试图确定SPARC如何调节依赖于转化生长因子-β1的信号转导。我们的数据表明，SPARC调节来自野生型和SPARC缺失小鼠的原代系膜细胞中依赖于转化生长因子-β1的Smad-2的磷酸化。我们还表明，SPARC通过增强转化生长因子-β1的刺激作用，调节系膜细胞中应激激活的c-jun-N末端激酶(JNK)的水平和激活。此外，我们还发现SPARC增加了转录因子c-jun的水平和活性。SPARC对转化生长因子-β1信号通路的这些作用似乎是通过与转化生长因子-β1受体复合体的相互作用来实现的，但仅在转化生长因子-β1与其同源的II型受体结合的情况下。SPARC直接参与了转化生长因子-β1信号通路的调控，这与基质细胞蛋白调节细胞、生长因子及其各自受体之间的相互作用的范式是一致的。(C)2004年Wiley-Liss公司
Secreted protein acidic and rich in cysteine (SPARC), a member of the family of matricellular proteins, regulates the interaction of cells with pleiotropic factors and proteins of the extracellular matrix (ECM). Although it has been appreciated that transforming growth factor beta 1 (TGF-beta1) induces SPARC and collagen type 1, we have recently shown that SPARC regulates the expression of TGF-beta1 and collagen type I in renal mesangial cells via a TGF-beta1-dependent pathway, and have proposed a reciprocal, autocrine regulatory feedback loop between SPARC and TGF-beta1. Herein, we sought to determine how SPARC regulates TGF-beta1-dependent signal transduction. Our data indicate that SPARC modulates the TGF-beta1-dependent phosphorylation of Smad-2 in primary mesangial cells derived from wild-type and SPARC-null mice. We also show that SPARC regulates the levels and activation of the stress-activated c-jun-N-terminal kinase (JNK) in mesangial cells by augmentation of the stimulatory effects of TGF-beta1. Furthermore, we found that SPARC increases the levels and the activity of the transcription factor c-jun. These effects of SPARC on the TGF-beta1 signaling pathway appear to he mediated through an interaction with the TGF-beta1-receptor complex, but only in the presence of TGF-beta1 bound to its cognate type II receptor. That SPARC is directly involved in the regulation of the TGF-beta1 signaling cascade is consistent with the paradigm that matricellular proteins modulate interactions among cells, growth factors, and their respective receptors. (C) 2004 Wiley-Liss, Inc.