成纤维细胞氨基酸代谢参与肺纤维化发生与发展

Amino acid metabolism of fibroblasts involved in the occurrence and development of pulmonary fibrosis

肺纤维化是多种肺部疾病的共有病理改变,其发病机制和特征主要是反复的肺泡损伤导致成纤维细胞异常活化引发大量细胞外基质堆积。成纤维细胞在健康肺组织中不仅负责构建完整的肺间质组分,也参与正常的损伤后修复进程。而在肺纤维化进程中的效应细胞,成纤维细胞向肌成纤维细胞分化后出现了典型的促纤维化代谢表型。由于肌成纤维细胞在大量合成胶原的过程中需要多种氨基酸原料,因此其氨基酸代谢出现了丝氨酸/甘氨酸、谷氨酰胺、脯氨酸、精氨酸代谢旺盛的特征。与此同时在羟脯氨酸形成过程中,肌成纤维细胞也获得了抵抗凋亡的能力。而作为分解胶原的重要细胞类型,成纤维细胞在清除胶原片段的过程中还可重新利用多种降解后的氨基酸进行细胞代谢,但若成纤维细胞自噬功能受到抑制,则大量细胞外基质无法得到有效清除,加剧了肺纤维化进程。本综述主要对于成纤维细胞氨基酸代谢表型对肺纤维化进程影响进行总结。

Pulmonary fibrosis is a common pathological change in many chronic lung diseases,and its pathogenesis and characteristics are mainly caused by repeated lung alveolar injury leading to abnormal activation of fibroblasts and the accumulation of large amounts of extracellular matrix(ECM)deposition.Fibroblasts are not only responsible for constituting the interstitial structure of the lung but are also involved in the post-injury repairment in healthy lung tissue.In contrast,fibroblasts show a typical pro-fibrotic metabolic phenotype after differentiation into myofibroblasts during the development of pulmonary fibrosis.To synthesis large amount of collagen,the myofibroblasts have a strong metabolism characteristic of serine/glycine,glutamine,proline,and arginine.At the same time,the myofibroblast get the ability to resist cell apoptosis.As an important cell type for collagen degradation,fibroblasts reuse the amino acids of collagen to maintain cell metabolism.However,the myofibroblasts cannot degrade the ECM due to the suppression of autophagy activity,thus accelerating the progression of pulmonary fibrosis.This review attempts to summarize how amino acid metabolism of fibroblasts influence the pulmonary fibrosis.