Kum Yoon-Seup, Kim Kyung-Hyun, Park Tae-In, Suh In-Soo, Oh Hoon-Kyu, Cho Chang-Ho, Park Jae-Bok, Chang Young-Chae, Park Ji-Hyun, Lee Kwang-Gil, Park Kwan-Kyu
Department of Pathology, Catholic University of Daegu, College of Medicine, 3056-6, Daemyung 4-Dong, Nam-Gu, Daegu 705-718, Republic of Korea.
Biochem Biophys Res Commun. 2007 Nov 16;363(2):368-74. doi: 10.1016/j.bbrc.2007.08.176. Epub 2007 Sep 10.
The aim of this study is to evaluate the antifibrotic effect of ring-type Sp1 decoy oligonucleotides (ODNs) through blocking the transcription of transforming growth factor (TGF)-beta1 and its downstream target genes. In this experiment, the expression of TGF-beta1, metalloproteinase (MMP)-13, and fibronectin was decreased in the group with the treatment of the ring-type Sp1 decoy ODNs. Also, alpha-smooth muscle actin positive bronchial lining cells and alveolar epithelial cells were observed, especially around the lesions of extracellular matrix (ECM) deposition. These findings provide evidences for the finding of pulmonary epithelial-mesenchymal transition (EMT) and the effectiveness of Sp1 transcription factor as a target for the gene therapy on lung fibrosis.
本研究的目的是通过阻断转化生长因子(TGF)-β1及其下游靶基因的转录来评估环状Sp1诱饵寡核苷酸(ODNs)的抗纤维化作用。在本实验中,环状Sp1诱饵ODNs处理组中TGF-β1、金属蛋白酶(MMP)-13和纤连蛋白的表达降低。此外,观察到α-平滑肌肌动蛋白阳性的支气管内衬细胞和肺泡上皮细胞,尤其是在细胞外基质(ECM)沉积病变周围。这些发现为肺上皮-间质转化(EMT)的发现以及Sp1转录因子作为肺纤维化基因治疗靶点的有效性提供了证据。