TGF-β抑制剂(Decorin)抗滤过泡瘢痕形成及毒副作用的实验研究

目的 观察Decorin抑制结膜瘢痕形成 ,降低眼压效果和对兔眼的毒副作用。方法 模型采用Reichel结膜瘢痕模型 ,Schiotz氏眼压计测量眼压变化 ,结合光镜、电镜观察兔眼病理改变。结果 Decorin可使滤过泡形态良好 ,维持较长时间低眼压 ,而且无毒副作用。结论 Decorin可作为抑制滤过泡瘢痕形成的辅助药物之一。

TGF-β抑制剂SB-431542对支气管哮喘小鼠气道重塑的干预作用

目前认为气道重塑是除气道慢性炎性反应之外哮喘的另一个重要特征。气道重塑不仅导致不可逆性的气流阻塞而增加气道阻力﹑加重气道高反应性,进而导致严重的肺功能低下。目前治疗和预防哮喘的有效药物是糖皮质激素,它虽然能抑制炎性反应、减轻症状,但不能逆转已形成的气道结构改变,

Smad3 mediates immediate early induction of Idl by TGF-β

Idl is a member of the inhibitor of differentiation （Id） protein family that regulates a wide range of cell functions. Previous studies have shown that expression of the Idl gene is down-regulated by TGF-β in epithelial cells, whereas it is up-regulated by BMP in a variety of cell types. During our study of the biological function of TGF-β1, we found that Idl can be strongly up-regulated by TGF-β1 in the human mammary gland epithelial cell line MCF10A. Quantitative real-time RT-PCR has revealed as high as 7.5-fold induction ofldl mRNA by TGF-β1 in MCF10A cells after 1 h of TGF-β1 stimulation, and this induction does not require de novo protein synthesis. Using Smad knockdown and knockout approaches, we have identified Smad3 as the responsible R-Smad for mediating transcriptional activation of the Idl gene. Chromatin immunoprecipitation assay confirms that Smad3 and Smad4 bind to the upstream region of the Idl gene. Our results demonstrate that Smad3, but not Smad2, mediates TGF-β1-dependent early transcriptional induction of Idl.

转化生长因子-β抑制剂研究进展

转化生长因子-β(transforming growth factor-β,TGF-β)是生物体内重要的细胞因子,具有多种生物学效应,包括胚胎发育、伤口愈合、趋化作用和细胞周期调控等。上皮-间质转化(EMT)是肿瘤细胞获得侵袭和转移能力的最主要途径,而TGF-β是已知诱导肿瘤细胞发生EMT的关键因子,对肿瘤的发生、转移等起着非常重要作用。近年来对TGF-β抑制剂的研究取得了一些进展,已经有部分药物上市和进入临床研究,在肿瘤的治疗、疤痕修复、青光眼治疗和肝肾的纤维化疾病治疗等方面有广泛应用。本文主要对近年来设计合成的新型TGF-β抑制剂进行综述。