Gene expression profiling of familial and sporadic interstitial pneumonia
Gene expression profiling of familial and sporadic interstitial pneumonia
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DOI：
10.1164/rccm.200601-062oc
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发表时间：
2007-01-01
影响因子：
24.7
通讯作者：
Schwartz, David A.
中科院分区：
文献类型：
--
作者：
Yang, Ivana V.;Burch, Lauranell H.;Schwartz, David A.
理论基础：特发性间质性肺炎(IIP)及其家族性变异是进行性的、大部分无法治疗的疾病，其分子机制知之甚少。目的：研究家族性和非家族性普通型间质性肺炎和非特异性间质性肺炎患者肺组织中基因的表达，并与正常肺组织中的基因表达进行比较。方法：在人类全基因组寡核苷酸微阵列上对16例散发性间质性肺炎患者、10例家族性髋关节患者和9例正常对照组肺组织的RNA进行分析。区分基因亚型的基因与区分唇部和正常样本的转录本属于相同的功能类别。相关类别包括趋化因子和生长因子及其受体、补体成分、与细胞增殖和死亡相关的基因以及Wnt途径中的基因。趋化因子CXCL12在博莱霉素肺损伤小鼠模型中的作用得到证实，C57BL/6(CXCR4+/-)小鼠的胶原沉积明显少于C57BL/(6XCR4+/+)小鼠。家族性和散发性间质性肺炎之间存在显著差异，而普通型间质性肺炎和非特异性间质性肺炎之间仅有微小的基因表达变化。结论：家族性和散发性间质性肺炎之间的基因表达谱差异可能为IIP的病因和发病机制提供线索。
Rationale: Idiopathic interstitial pneumonia (IIP) and its familial variants are progressive and largely untreatable disorders with poorly understood molecular mechanisms. Both the genetics and the histologic type of IIP play a role in the etiology and pathogenesis of interstitial lung disease, but transcriptional signatures of these sub-types are unknown.Objectives: To evaluate gene expression in the lung tissue of patients with usual interstitial pneumonia or nonspecific interstitial pneumonia that was either familial or nonfamilial in origin, and to compare it with gene expression in normal lung parenchyma.Methods: We profiled RNA from the lungs of 16 patients with sporadic IIP, 10 with familial HIP, and 9 normal control subjects on a whole human genome oligonucleotide microarray.Results: Significant transcriptional differences exist in familial and sporadic lips. The genes distinguishing the genetic subtypes belong to the same functional categories as transcripts that distinguish lip from normal samples. Relevant categories include chemokines and growth factors and their receptors, complement components, genes associated with cell proliferation and death, and genes in the Wnt pathway. The role of the chemokine CXCL12 in disease pathogenesis was confirmed in the murine bleomycin model of lung injury, with C57BL/6(CXCR4+/-) mice demonstrating significantly less Collagen deposition than C57BL/(6XCR4+/+) mice. Whereas substantial differences exist between familial and sporadic IIPs, we identified only minor gene expression changes between usual interstitial pneumonia and nonspecific interstitial pneumonia .Conclusions: Taken together, our findings indicate that differences in gene expression profiles between familial and sporadic UPS may provide clues to the etiology and pathogenesis of IIP.