Departments of Cell Biology and Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
J Biochem. 2012 Oct;152(4):321-9. doi: 10.1093/jb/mvs089. Epub 2012 Aug 24.
The cytokine transforming growth factor-beta (TGF-β) has multiple effects in both physiological and pathological conditions. TGF-β is secreted as part of a tripartite complex from which it must be released in order to bind to its receptor. Sequestration of latent TGF-β in the extracellular matrix (ECM) is crucial for proper mobilization of the latent cytokine and its activation. However, contrary to expectation, loss-of-function mutations in genes encoding certain matrix proteins that bind TGF-β yield elevated, rather than decreased, TGF-β levels, posing a 'TGF-β paradox.' In this review, we discuss recent findings concerning the relationship of TGF-β, ECM molecules, and latent TGF-β activation and propose a model to resolve the 'TGF-β paradox.'
细胞因子转化生长因子-β（TGF-β）在生理和病理条件下具有多种作用。TGF-β 作为三部分复合物的一部分被分泌，为了与受体结合，它必须从复合物中释放出来。潜伏的 TGF-β在细胞外基质（ECM）中的隔离对于适当动员潜伏细胞因子及其激活至关重要。然而，与预期相反，编码某些与 TGF-β结合的基质蛋白的基因的功能丧失突变会导致 TGF-β水平升高，而不是降低，从而产生“TGF-β悖论”。在这篇综述中，我们讨论了关于 TGF-β、ECM 分子和潜伏 TGF-β激活之间关系的最新发现，并提出了一个模型来解决“TGF-β悖论”。
