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首页> 外文期刊>Cellular Physiology and Biochemistry >TIMP-1 Induces α-Smooth Muscle Actin in Fibroblasts to Promote Urethral Scar Formation
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TIMP-1 Induces α-Smooth Muscle Actin in Fibroblasts to Promote Urethral Scar Formation

机译：TIMP-1诱导成纤维细胞中的α-平滑肌肌动蛋白促进尿道瘢痕形成

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Background/Aims: Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been reported to upregulate in urethral scar. However, the underlying molecular mechanisms remain undefined. Methods: Here, we studied levels of TIMP-1 and α-smooth muscle actin (α-SMA) in the fibroblasts isolated from urethral scar tissues, compared to the fibroblasts isolated from normal urethra. Then we either overexpressed TIMP-1, or inhibited TIMP-1 by lentiviruses carrying a transgene or a short hairpin small interfering RNA for TIMP-1 in human fibroblasts. We examined the effects of modulation of TIMP-1 on α-SMA, and on epithelial-mesenchymal transition (EMT)-related genes. We also studied the underlying mechanisms. Results: We detected significantly higher levels of TIMP-1 and α-smooth muscle actin (α-SMA) in the fibroblasts isolated from urethral scar tissues, compared to the fibroblasts isolated from normal urethra. Moreover, the levels of TIMP-1 and α-SMA strongly correlated. Moreover, we found that TIMP-1 significantly increased levels of α-SMA, transforming growth factor β 1 (TGFβ1), Collagen I and some other key factors related to an enhanced EMT, suggesting that TIMP-1 may induce transformation of fibroblasts into myofibroblasts to promote tissue EMT to enhance the formation of urethral scar. Moreover, increases in TIMP-1 also induced an increase in fibroblast cell growth and cell invasion, in an ERK/MAPK-signaling-dependent manner. Conclusion: Our study thus highlights a pivotal role of TIMP-1 in urethral scar formation.
机译：背景/目的：据报道，金属蛋白酶-1（TIMP-1）的组织抑制剂在尿道瘢痕中上调。但是，潜在的分子机制仍然不确定。方法：在这里，我们研究了从尿道瘢痕组织分离的成纤维细胞与正常尿道分离的成纤维细胞相比，TIMP-1和α-平滑肌肌动蛋白（α-SMA）的水平。然后，我们要么通过携带人成纤维细胞中TIMP-1的转基因或短发夹状小干扰RNA的慢病毒来过表达TIMP-1，要么抑制TIMP-1。我们检查了TIMP-1的调制对α-SMA，以及上皮-间质转化（EMT）相关基因的影响。我们还研究了潜在的机制。结果：与从正常尿道分离的成纤维细胞相比，我们从尿道瘢痕组织分离的成纤维细胞中检测到TIMP-1和α-平滑肌肌动蛋白（α-SMA）的水平明显更高。此外，TIMP-1和α-SMA的水平强烈相关。此外，我们发现TIMP-1显着增加了α-SMA，转化生长因子β1（TGFβ1），胶原I和其他一些与EMT增强有关的关键因素，这表明TIMP-1可能诱导成纤维细胞转化为成肌纤维细胞促进组织EMT，增强尿道瘢痕的形成。此外，TIMP-1的增加还以ERK / MAPK信号依赖性方式诱导成纤维细胞生长和细胞侵袭的增加。结论：因此，我们的研究突出了TIMP-1在尿道瘢痕形成中的关键作用。

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