miR-338-5p调控肺成纤维细胞LPA1基因表达对肺纤维化的影响及机制研究

肺纤维化缺乏有效治疗手段，预后极差。我们在前期对肺纤维化大鼠肺组织进行microRNA芯片分析，发现miR-338-5p表达下降，采用生物信息学方法发现溶血磷脂酸受体1（LAP1）基因的3'-UTR序列含有miR-338-5p结合位点，提高大鼠肺成纤维细胞miR-338-5p水平可以降低其LPA1蛋白表达，而对LPA1mRNA表达无明显影响，提示miR-338-5p可能通过转录后调控抑制重要致纤维化靶基因LPA1的表达。本课题拟通过调控人肺成纤维细胞和动物肺纤维化模型的miR-338-5p表达，观察人肺成纤维细胞表型的变化，对miR-338-5p与肺纤维化的关系进行初步探讨。通过研究miR-338-5p对LPA1的调控机制及其是否通过LPA1调控肺成纤维细胞表型和功能改变，进一步了解miR-338-5p在肺纤维化过程中可能的调控机制。本项目可能为肺纤维化的治疗提供新的干预靶点。

Pulmonary fibrosis is lack of effective treatment and the prognosis is very poor. In our previous microRNA microarray analysis with lung tissues in pulmonary fibrosis rat models, the expression of miR-338-5p decreased. We predicted the target genes of miR-338-5p by the means of the bioinformatics methods and found that the 3'-UTR sequence of lysophosphatidic acid receptor 1 (LPA1) gene contained the binding site of miR-338-5p. The protein of LPA1 decreased in rat lung fibroblasts as the expression of miR-338-5p was elevated while LPA1 mRNA expression remained constant, suggesting that miR-338-5p may inhibit the expression of the important profibrogenic gene LPA1 through regulating post transcriptional modulation. The present research is proposed to observe the phenotypic changes of human lung fibroblasts in the way of regulating the miR-338-5p expressions in human lung fibroblasts and animal pulmonary fibrosis models as well as to further understand the possible regulation mechanism of miR-338-5p in the process of pulmonary fibrosis through studying the regulation mechanism of miR-338-5p on LPA1 and if miR-338-5p regulates the phenotypic and functional changes of lung fibroblasts by regulating LPA1 expression. The present research may provide novel target for the therapy of pulmonary fibrosis.