慢性肾脏病已成为危害人类健康的全球性公共卫生难题。以线粒体为中心的能量代谢是细胞维持正常结构和功能的基础。作为肾功能进行性衰竭的根本原因，肾小管间质纤维化与细胞能量代谢的异常密切相关。本项目从细胞能量代谢角度，以肾间质纤维化模型及相关的肾小管上皮细胞、间质成纤维细胞及巨噬细胞为研究对象，通过比较正常和疾病状态下肾小管间质和上述细胞的能量代谢特点，重点探讨不同条件下细胞能量代谢方式的转换/重组与间质纤维化的关系，并以解耦联蛋白为靶标探索线粒体代谢在此之中的作用与相关调控机制。本项目试图通过探讨细胞能量代谢在小管间质纤维化中的作用，为进一步深入认识肾间质纤维化的病理生理机制及未来设计全新的防治肾间质纤维化的治疗方案提供理论基础。

Chronic kidney disease (CKD) has now emerged as a global public health burden. As the final common result of all kidney diseases leading to chronic renal failure, it has recently been postulated that renal tubulointerstitial fibrosis may suffer from energy metabolic derangements. However, much remains unknown. In this study, we will focus on the role and mechanism of energy metabolic derangements in the progression of renal fibrosis. By comparing metabolic characteristics under normal and pathophysiological conditions, we investigate the existence of metabolic reprogramming and its relevance to renal tubulointerstitial fibrosis. Then, we would further explore the role of mitochondria in the modulation of metabolic reprogramming. Meanwhile, we would evaluate whether the mitochondrial uncoupling protein 2 (UCP2) could be the target protein to control metabolic reprogramming and renal tubulointerstitial fibrosis. This study will not only be help for understanding the pathogenesis of renal tubulointerstitial fibrosis, but also provide the theoretical basis to design the novel remedy to prevent the progression for chronic kidney disease.