Department of Dermatology and Venerology, Beijing Military Command General Hospital of PLA, China.
Biochem Biophys Res Commun. 2011 Aug 12;411(4):821-5. doi: 10.1016/j.bbrc.2011.07.044. Epub 2011 Jul 21.
The transforming growth factor-β (TGF-β) signaling pathway plays a key role in the fibrotic process in systemic scleroderma (SSc). Curcumin, a Turmeric root extract, has been demonstrated to exert antifibrotic activity. In the present study, we carefully investigated the effect of curcumin on TGF-β signaling and its potential mechanism in SSc fibroblasts. We demonstrated a potent inhibitory effect of curcumin on TGF-β signaling. Curcumin counteracted TGF-β-induced phosphorylation of Smad2 but not Smad3. Further study revealed curcumin induced upregulation of TGF-β-induced factor (TGIF), a negative regulator of TGF-β signaling. The TGIF silencing results evidenced the essential role of TGIF in curcumin-mediated TGF-β/Smad2 suppression. Moreover, our data indicated that the upregulation of TGIF by curcumin might result from decreased ubiquitination of TGIF, which blocks its proteasome-mediated degradation. Collectively, our data provide a novel mechanism of curcumin-mediated suppression of fibrotic process in scleroderma.
转化生长因子-β（TGF-β）信号通路在系统性硬皮病（SSc）的纤维化过程中发挥着关键作用。姜黄素，一种姜黄根提取物，已被证明具有抗纤维化活性。在本研究中，我们仔细研究了姜黄素对 SSc 成纤维细胞中 TGF-β 信号的影响及其潜在机制。我们证明了姜黄素对 TGF-β 信号有很强的抑制作用。姜黄素拮抗 TGF-β诱导的 Smad2 磷酸化，但不拮抗 Smad3。进一步的研究揭示了姜黄素诱导 TGF-β诱导因子（TGIF）的上调，TGIF 是 TGF-β 信号的负调节剂。TGIF 沉默的结果证明了 TGIF 在姜黄素介导的 TGF-β/Smad2 抑制中的重要作用。此外，我们的数据表明，姜黄素诱导的 TGIF 上调可能是由于 TGIF 的泛素化减少，从而阻止了其蛋白酶体介导的降解。总之，我们的数据提供了姜黄素抑制硬皮病纤维化过程的新机制。
