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Druggability of lipid metabolism modulation against renal fibrosis

期刊

ACTA PHARMACOLOGICA SINICA
卷 43, 期 3, 页码 505-519

出版社

NATURE PUBL GROUP
DOI: 10.1038/s41401-021-00660-1

关键词

lipid metabolism; anti-renal fibrosis; drug targets; fatty acid oxidation; noncoding RNA

资金

  1. Drug Innovation Major Project of China [2018ZX09711001-002-010]
  2. Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences [2016-I2M-3-011]
  3. Beijing Natural Science Foundation [7202138, 7181007]

向作者/读者索取更多资源

Renal fibrosis, a common pathological process in chronic kidney disease leading to kidney failure, lacks effective drugs for treatment. Dysfunctional lipid metabolism exacerbates chronic kidney disease and fibrosis, while restoring fatty acid oxidation may alleviate renal fibrosis.
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.

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