Lung fibrotic tenascin-C upregulation is associated with other extracellular matrix proteins and induced by TGFβ1.
Lung fibrotic tenascin-C upregulation is associated with other extracellular matrix proteins and induced by TGFβ1.
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DOI：
10.1186/1471-2466-14-120
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发表时间：
2014-07-26
影响因子：
3.1
通讯作者：
Molina-Molina M
中科院分区：
文献类型：
--
作者：
Estany S;Vicens-Zygmunt V;Llatjós R;Montes A;Penín R;Escobar I;Xaubet A;Santos S;Manresa F;Dorca J;Molina-Molina M
特发性肺纤维化（IPF）是一种病因不明、预后不良的进行性肺实质疾病，其特征是组织修复和纤维化改变。细胞外基质（ECM）是调节细胞稳态和适当伤口愈合的关键组分。我们研究的目的是确定IPF肺中突出显示的ECM蛋白的表达谱。通过cDNA微阵列、rt-PCR、免疫组化和western-blot分析特发性肺纤维化（IPF）、过敏性肺炎（HP）（分为慢性（cHP）和亚急性（saHP））和健康肺组织中ECM基因和蛋白的表达。研究了来自正常受试者和纤维化患者的原代成纤维细胞培养物以评估腱生蛋白-C（TNC）合成。IPF中共有20种ECM蛋白表达上调，6种蛋白表达下调。与saHP相比，TNC在正常肺中几乎未检测到，在纤维化肺（IPF和cHP）中显著上调。此外，它特异性地位于纤维化肺的成纤维细胞灶区域，具有上皮下梯度模式。TNC水平与cHP肺中的成纤维细胞灶含量相关。Versican和纤连蛋白糖蛋白与TNC相关，主要在纤维化肺的成纤维细胞灶中。来自IPF患者的成纤维细胞组成性地合成比正常成纤维细胞更高水平的TNC。TGF-β1可诱导纤维化和正常成纤维细胞产生TNC和α-sma。正常和纤维化成纤维细胞的TNC处理诱导了α-sma mRNA的非显著增加。间质性肺疾病中ECM糖蛋白含量的差异可能有助于肺纤维化的发展。纤维化活性的间质区域中TNC的增加可能在改变的伤口愈合中起关键作用。
Idiopathic pulmonary fibrosis (IPF) is a progressive parenchymal lung disease of unknown aetiology and poor prognosis, characterized by altered tissue repair and fibrosis. The extracellular matrix (ECM) is a critical component in regulating cellular homeostasis and appropriate wound healing. The aim of our study was to determine the expression profile of highlighted ECM proteins in IPF lungs. ECM gene and protein expression was analyzed by cDNA microarrays, rt-PCR, immunohistochemistry and western-blot in lungs from idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP), categorized as chronic (cHP) and subacute (saHP), and healthy lung tissue. Primary fibroblast cultures from normal subjects and fibrotic patients were studied to evaluate tenascin-C (TNC) synthesis. A total of 20 ECM proteins were upregulated and 6 proteins downregulated in IPF. TNC was almost undetected in normal lungs and significantly upregulated in fibrotic lungs (IPF and cHP) compared to saHP. Furthermore, it was located specifically in the fibroblastic foci areas of the fibrotic lung with a subepithelial gradient pattern. TNC levels were correlated with fibroblastic foci content in cHP lungs. Versican and fibronectin glycoproteins were associated with TNC, mainly in fibroblastic foci of fibrotic lungs. Fibroblasts from IPF patients constitutively synthesized higher levels of TNC than normal fibroblasts. TNC and α-sma was induced by TGF-β1 in both fibrotic and normal fibroblasts. TNC treatment of normal and fibrotic fibroblasts induced a non-significant increased α-sma mRNA. The difference in ECM glycoprotein content in interstitial lung diseases could contribute to the development of lung fibrosis. The increase of TNC in interstitial areas of fibrotic activity could play a key role in the altered wound healing.
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影响因子：
7.3
作者：
Matsushita, MD;da Silva, LFF;Dolhnikoff, M
通讯作者：
Dolhnikoff, M
DOI：
10.1111/j.1365-2613.2010.00743.x
发表时间：
2011-02-01
影响因子：
3
作者：
Fitch, Paul M.;Howie, Sarah E. M.;Wallace, William A. H.
通讯作者：
Wallace, William A. H.
DOI：
10.1164/ajrccm.154.2.8756830
发表时间：
1996-08-01
影响因子：
24.7
作者：
KaarteenahoWiik, R;Tani, T;Paakko, P
通讯作者：
Paakko, P
DOI：
10.1164/rccm.2009-040gl
发表时间：
2011-03-15
影响因子：
24.7
作者：
Raghu, Ganesh;Collard, Harold R.;Schuenemann, Holger J.
通讯作者：
Schuenemann, Holger J.
影响因子：
6
作者：
Nagaharu, Keiki;Zhang, Xinhui;Imanaka-Yoshida, Kyoko
通讯作者：
Imanaka-Yoshida, Kyoko