State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union medical college, Beijing, 100050, China.
Acta Pharmacol Sin. 2022 Mar;43(3):505-519. doi: 10.1038/s41401-021-00660-1. Epub 2021 May 14.
Renal fibrosis contributes to progressive damage to renal structure and function. It is a common pathological process as chronic kidney disease develops into kidney failure, irrespective of diverse etiologies, and eventually leads to death. However, there are no effective drugs for renal fibrosis treatment at present. Lipid aggregation in the kidney and consequent lipotoxicity always accompany chronic kidney disease and fibrosis. Numerous studies have revealed that restoring the defective fatty acid oxidation in the kidney cells can mitigate renal fibrosis. Thus, it is an important strategy to reverse the dysfunctional lipid metabolism in the kidney, by targeting critical regulators of lipid metabolism. In this review, we highlight the potential "druggability" of lipid metabolism to ameliorate renal fibrosis and provide current pre-clinical evidence, exemplified by some representative druggable targets and several other metabolic regulators with anti-renal fibrosis roles. Then, we introduce the preliminary progress of noncoding RNAs as promising anti-renal fibrosis drug targets from the perspective of lipid metabolism. Finally, we discuss the prospects and deficiencies of drug targeting lipid reprogramming in the kidney.
肾纤维化导致肾脏结构和功能进行性损伤。它是一种常见的病理过程,随着慢性肾脏病发展为肾衰竭,无论病因如何,最终都会导致死亡。然而,目前尚无有效的肾纤维化治疗药物。肾脏中的脂质聚集和随之而来的脂毒性总是伴随着慢性肾脏病和纤维化。大量研究表明,恢复肾脏细胞中缺陷的脂肪酸氧化可以减轻肾纤维化。因此,通过针对脂质代谢的关键调节因子来逆转肾脏中功能失调的脂质代谢是一种重要的策略。在这篇综述中,我们强调了改善肾纤维化的脂质代谢的潜在“可药性”,并提供了当前的临床前证据,以一些有代表性的可药物靶点和其他几种具有抗肾纤维化作用的代谢调节剂为例。然后,我们从脂质代谢的角度介绍了非编码 RNA 作为有前途的抗肾纤维化药物靶点的初步进展。最后,我们讨论了靶向肾脏脂质重编程的前景和局限性。