Renal fibrosis is a common and irreversible pathological feature of end-stage renal disease caused by multiple etiologies. The role of inflammation in renal fibrosis tissue has been generally accepted. The latest view is that fatty acid metabolism disorder contributes to renal fibrosis. peroxisome proliferator activated receptor-gamma coactivator 1α (PGC1α) plays a key role in fatty acid metabolism, regulating fatty acid uptake and oxidized protein synthesis, preventing the accumulation of lipid in the cytoplasm, and maintaining a dynamic balanced state of intracellular lipid. In multiple animal models of renal fibrosis caused by acute or chronic kidney disease, or even age-related kidney disease, almost all of the kidney specimens show the down-regulation of PGC1α. Upregulation of PGC1α can reduce the degree of renal fibrosis in animal models, and PGC1α knockout animals exhibit severe renal fibrosis. Studies have demonstrated that AMP-activated protein kinase (AMPK), MAPK, Notch, tumor necrosis factor-like weak inducer of apoptosis (TWEAK), epidermal growth factor receptor (EGFR), non-coding RNA (ncRNAs), liver kinase B1 (LKB1), hairy and enhancer of split 1 (Hes1), and other pathways regulate the expression of PGC1α and affect fatty acid metabolism. But some of these pathways interact with each other, and the effect of the integrated pathway on renal fibrosis is not clear.
肾纤维化是多种病因引起终末期肾病不可逆的共同病理特征。炎症对肾纤维化的作用已被普遍认可，最新的观点认为脂肪酸代谢障碍亦是导致肾纤维化的重要因素。过氧化物酶体增殖物激活受体γ共同激活剂1α(peroxisome proliferator activated receptor-gamma coactivator 1α，PGC1α)是脂肪酸代谢的关键基因，它调节脂肪酸摄取和氧化蛋白质的合成，促进脂肪酸在细胞内的分解代谢，防止脂质在细胞质内蓄积，使细胞内脂质处于动态平衡状态。在各种急、慢性肾病甚至老龄引起的肾纤维化动物模型中，几乎都可观察到肾组织内PGC1α表达下降。促进PGC1α表达可减轻动物模型肾纤维化程度，而敲除PGC1α基因的动物模型表现出严重的肾纤维化。已有研究表明AMP活化的蛋白激酶(AMP-activated protein kinase，AMPK)、MAPK、Notch、肿瘤坏死因子样凋亡的弱诱导剂(tumor necrosis factor-like weak inducer of apoptosis，TWEAK)、表皮生长因子受体(epidermal growth factor receptor，EGFR)、非编码RNA(non-coding RNA，ncRNAs)、肝激酶B1(liver kinase B1，LKB1)及发状分裂相关增强子1(hairy and enhancer of split 1，Hes1)等通路可通过调节PGC1α表达影响脂肪酸代谢，其中一些通路之间存在相互作用，整合后的通路对肾纤维化的影响尚不明确。.
Keywords: fatty acid metabolism; peroxisome proliferator-actinated receptor gamma coactivator 1α; renal fibrosis.