Zhu Xuyou, Fang Xia, Chen Wei, Han Fei, Huang Ziling, Luo Benfang, Gu Pan, Zhang Long, Qiu Weizhe, Zeng Yu, Rui Weiwei, Yi Xianghua
Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
Department of Hematology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.
J Thorac Dis. 2017 Mar;9(3):519-528. doi: 10.21037/jtd.2017.02.50.
Idiopathic nonspecific interstitial pneumonia (INSIP) presents with varying degrees of interstitial inflammation and fibrosis exhibiting a uniform appearance. Lack of knowledge on the underlying mechanisms of INSIP has contributed to few effective treatment strategies. Our study is designed to explore aberrantly expressed cytokines involvement in INSIP development.
Oligo GEArray was employed to detect the expression of cytokines in INSIP patients, and idiopathic pulmonary fibrosis (IPF) was setup as isotype control. Real-time PCR and immunohistochemistry analysis were used to further confirm the expression of abnormally expressed cytokines. The correlationship between cytokines expression and overall survival rate of patients with IPF and INSIP were analyzed.
From microarray detection, transforming growth factor-beta-1 (TGF-β1), fibroblast growth factor 10 (FGF10), and platelet derived growth factor (PDGF) were predominantly up-regulated in patients with INSIP. Real-time PCR and immunohistochemistry also showed these cytokines was abnormally expressed in INSIP. In addition to, the clinical relevance analysis demonstrated relatively lower expression of PDGF patients had longer overall survival rate than those with higher expression of PDGF.
Our study suggests that TGF-β1, FGF10, and PDGF are required for the pathogenesis of INSIP, and may therefore be ideal targets in INSIP treatment. Moreover, INSIP patients with lower expression of PDGF had better survival rate.
特发性非特异性间质性肺炎(INSIP)表现为不同程度的间质性炎症和纤维化,呈现出一致的外观。对INSIP潜在机制的认识不足导致有效的治疗策略较少。我们的研究旨在探讨异常表达的细胞因子在INSIP发病机制中的作用。
采用寡核苷酸基因芯片检测INSIP患者细胞因子的表达,并将特发性肺纤维化(IPF)作为同型对照。采用实时荧光定量PCR和免疫组织化学分析进一步证实异常表达细胞因子的表达。分析细胞因子表达与IPF和INSIP患者总生存率的相关性。
通过基因芯片检测,转化生长因子-β1(TGF-β1)、成纤维细胞生长因子10(FGF10)和血小板衍生生长因子(PDGF)在INSIP患者中主要上调。实时荧光定量PCR和免疫组织化学也显示这些细胞因子在INSIP中异常表达。此外,临床相关性分析表明,PDGF表达相对较低的患者总生存率高于PDGF表达较高的患者。
我们的研究表明,TGF-β1、FGF10和PDGF是INSIP发病机制所必需的,因此可能是INSIP治疗的理想靶点。此外,PDGF表达较低的INSIP患者生存率更高。