The Wnt antagonist Wif‐1 interacts with CTGF and inhibits CTGF activity
The Wnt antagonist Wif‐1 interacts with CTGF and inhibits CTGF activity
复制标题
DOI：
10.1002/jcp.22957
复制
发表时间：
2012-05
影响因子：
5.6
通讯作者：
C. Surmann-Schmitt;Takako Sasaki;T. Hattori;Nicole Eitzinger;G. Schett;K. von der Mark;M. Stock
中科院分区：
文献类型：
--
作者：
C. Surmann-Schmitt;Takako Sasaki;T. Hattori;Nicole Eitzinger;G. Schett;K. von der Mark;M. Stock
Wnt抑制因子1（Wif-1）是Wnt信号传导的分泌型拮抗剂。我们最近证实，这种分子主要在骺软骨的浅层表达，但也在骨和肌腱中表达。此外，我们发现Wif-1能够与几种软骨相关的Wnt配体结合，并干扰软骨形成细胞中Wnt 3a依赖性Wnt信号传导。在这里，我们提供的证据表明，Wif-1的生物学功能可能不仅限于Wnt信号转导的调节，而且似乎包括其他信号转导途径的调节。因此，我们表明Wif-1在体外与结缔组织生长因子（CTGF/CCN 2）物理结合，主要是通过与CTGF的C末端半胱氨酸结结构域相互作用。在体内，这种相互作用似乎也有可能，因为这两种分泌的蛋白质的表达模式在骺软骨的外周区重叠。在软骨细胞中，CTGF已显示诱导软骨基质基因如聚集蛋白聚糖（Acan）和胶原2a 1（Col 2a 1）的表达。在这项研究中，我们证明了Wif-1能够干扰原代小鼠软骨细胞中Acan和Col 2a 1基因表达的CTGF依赖性诱导。相反，CTGF不干扰Wnt信号传导的Wif-1依赖性抑制。这些结果表明，Wif-1可能是软骨隔室中信号通路的多功能调节剂。J.细胞。227：2207-2216，2012。© 2011 Wiley Periodicals，Inc.
Wnt inhibitory factor 1 (Wif‐1) is a secreted antagonist of Wnt signalling. We recently demonstrated that this molecule is expressed predominantly in superficial layers of epiphyseal cartilage but also in bone and tendon. Moreover, we showed that Wif‐1 is capable of binding to several cartilage‐related Wnt ligands and interferes with Wnt3a‐dependent Wnt signalling in chondrogenic cells. Here we provide evidence that the biological function of Wif‐1 may not be confined to the modulation of Wnt signalling but appears to include the regulation of other signalling pathways. Thus, we show that Wif‐1 physically binds to connective tissue growth factor (CTGF/CCN2) in vitro, predominantly by interaction with the C‐terminal cysteine knot domain of CTGF. In vivo such an interaction appears also likely since the expression patterns of these two secreted proteins overlap in peripheral zones of epiphyseal cartilage. In chondrocytes CTGF has been shown to induce the expression of cartilage matrix genes such as aggrecan (Acan) and collagen2a1 (Col2a1). In this study we demonstrate that Wif‐1 is capable to interfere with CTGF‐dependent induction of Acan and Col2a1 gene expression in primary murine chondrocytes. Conversely, CTGF does not interfere with Wif‐1‐dependent inhibition of Wnt signalling. These results indicate that Wif‐1 may be a multifunctional modulator of signalling pathways in the cartilage compartment. J. Cell. Physiol. 227: 2207–2216, 2012. © 2011 Wiley Periodicals, Inc.