Localized expression of tenascin in systemic sclerosis-associated pulmonary fibrosis and its regulation by insulin-like growth factor binding protein 3.
Localized expression of tenascin in systemic sclerosis-associated pulmonary fibrosis and its regulation by insulin-like growth factor binding protein 3.
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DOI：
10.1002/art.30647
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发表时间：
2012-01
影响因子：
--
通讯作者：
Feghali-Bostwick, Carol A.
中科院分区：
文献类型：
--
作者：
Brissett, Monique;Veraldi, Kristen L.;Pilewski, Joseph M.;Medsger, Thomas A., Jr.;Feghali-Bostwick, Carol A.
腱生蛋白（TN）-C是一种与损伤和重塑相关的细胞外基质蛋白。由于转化生长因子（TGF）-β诱导TN-C和胰岛素样生长因子结合蛋白（IGFBP）-3，我们试图确定IGFBP-3在介导TGF-β对TN-C产生的作用中的作用，并评估SSc相关肺纤维化（PF）中TN-C的体内水平。在存在或不存在特异性siRNA和化学信号级联抑制剂的情况下，用TGF-β或IGFBP-3刺激原代人肺成纤维细胞。采用免疫组化（IHC）检测系统性硬化症（SSc）相关肺纤维化患者肺组织中TN-C水平，并与正常供体进行比较。TN-C水平定量血清中正常供体和SSc患者与PF或不使用ELISA。IGFBP-3介导TGF-β诱导TN-C。IGFBP-3以p38 K依赖性方式直接诱导TN-C。SSc肺组织中TN-C水平丰富，并定位于远端气道的上皮下层。近端气道周围未检测到TN-C。与没有这种并发症的患者相比，患有Ssc相关肺纤维化的患者的循环TN-C水平显著更高。在PF发作前后从SSc患者中获得的纵向样本显示PF后水平增加。在纤维化肺中过表达的IGFBP-3诱导上皮下成纤维细胞产生TN-C。肺组织中TN-C水平的升高与SSc和肺纤维化患者血清中TN-C水平的升高平行，表明TN-C可能是SSc-PF的有用生物标志物。
Tenascin (TN)-C is an extracellular matrix protein associated with injury and remodeling. Since Transforming Growth Factor (TGF)-β induces both TN-C and Insulin-Like Growth Factor Binding Protein (IGFBP)-3, we sought to determine the role of IGFBP-3 in mediating TGF-β’s effects on TN-C production and to assess the levels of TN-C in vivo in SSc-associated pulmonary fibrosis (PF). Primary human lung fibroblasts were stimulated with TGF-β or IGFBP-3 in the presence or absence of specific siRNAs and chemical signaling cascade inhibitors. TN-C levels were examined in lung tissues of patients with Systemic Sclerosis (SSc)-associated pulmonary fibrosis using immunohistochemistry (IHC) and compared to those of normal donors. TN-C levels were quantified in serum from normal donors and patients with SSc with or without PF using ELISA. IGFBP-3 mediated TGF-β induction of TN-C. Direct induction of TN-C by IGFBP-3 occurred in a p38K-dependent manner. TN-C levels were abundant in SSc lung tissues and localized to subepithelial layers of the distal airways. No TN-C was detectable around proximal airways. Patients with SSc-associated pulmonary fibrosis had significantly greater levels of circulating TN-C compared to patients without this complication. Longitudinal samples obtained from patients with SSc before and after the onset of PF showed increased levels post-PF. IGFBP-3, which is overexpressed in fibrotic lungs, induces production of TN-C by subepithelial fibroblasts. The increased lung tissue levels of TN-C parallel levels detected in sera of patients with SSc and lung fibrosis, suggesting that TN-C may be a useful biomarker for SSc-PF.
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影响因子：
4.8
作者：
Verrecchia, F;Chu, ML;Mauviel, A
通讯作者：
Mauviel, A
DOI：
10.1083/jcb.107.6.2757
发表时间：
1988-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mackie EJ;Halfter W;Liverani D
通讯作者：
Liverani D
影响因子：
6
作者：
Pilewski, JM;Liu, LX;Feghali-Bostwick, CA
通讯作者：
Feghali-Bostwick, CA
DOI：
10.1513/pats.200601-004tk
发表时间：
2006-06-01
期刊：
Proceedings of the American Thoracic Society
影响因子：
--
作者：
Willis, Brigham C;duBois, Roland M;Borok, Zea
通讯作者：
Borok, Zea
影响因子：
7.8
作者：
CHIQUET, M;FAMBROUGH, DM
通讯作者：
FAMBROUGH, DM