George Mason University, Department of Molecular and Microbiology, Manassas, VA 20110, USA.
Genomics. 2010 Sep;96(3):134-45. doi: 10.1016/j.ygeno.2010.04.005. Epub 2010 May 6.
Activated fibroblasts are the central effector cells of the progressive fibrotic process in idiopathic pulmonary fibrosis (IPF). Characterizing the genomic phenotype of isolated fibroblasts is essential to understanding IPF pathogenesis. Comparing the genomic phenotype of non-cultured pulmonary fibroblasts from advanced IPF patients' and normal lungs revealed novel genes, biological processes and concomitant pathways previously unreported in IPF fibroblasts. We demonstrate altered expression in proteasomal constituents, ubiquitination-mediators, Wnt, apoptosis and vitamin metabolic pathways and cell cycle regulators, suggestive of loss of cellular homeostasis. Specifically, FBXO32, CXCL14, BDKRB1 and NMNAT1 were up-regulated, while RARA and CDKN2D were down-regulated. Paradoxically, pro-apoptotic inducers TNFSF10, BAX and CASP6 were also found to be increased. This comprehensive description of altered gene expression in isolated IPF fibroblasts underscores the complex biological processes characteristic of IPF and may provide a foundation for future research into this devastating disease.
活化的成纤维细胞是特发性肺纤维化（IPF）进行性纤维化过程中的核心效应细胞。对分离的成纤维细胞的基因组表型进行特征分析对于理解 IPF 的发病机制至关重要。比较晚期 IPF 患者和正常肺中未培养的肺成纤维细胞的基因组表型，揭示了先前在 IPF 成纤维细胞中未报道的新基因、生物学过程和伴随的途径。我们证明了蛋白酶体成分、泛素化介体、Wnt、细胞凋亡和维生素代谢途径以及细胞周期调节剂的表达发生改变，提示细胞内稳态的丧失。具体而言，FBXO32、CXCL14、BDKRB1 和 NMNAT1 上调，而 RARA 和 CDKN2D 下调。矛盾的是，促凋亡诱导剂 TNFSF10、BAX 和 CASP6 也被发现增加。对分离的 IPF 成纤维细胞中改变的基因表达的全面描述强调了 IPF 的复杂生物学过程，并可能为未来对这种毁灭性疾病的研究提供基础。
