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Druggability of lipid metabolism modulation against renal fibrosis

Abstract

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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Fig. 1: The pathological progress in renal fibrosis.
Fig. 2: Brief overview of classical TGF-β pathway in renal fibrosis.
Fig. 3: Critical lipid metabolism regulators with potential druggability in the kidney fibrosis discussed in the current review.
Fig. 4: MiRNA/lncRNA performs as upstream mediators to influence renal fibrosis in an epigenetic way.

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Funding

This paper was supported by the Drug Innovation Major Project of China [grant number 2018ZX09711001-002-010]; Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences [grant number 2016-I2M-3–011]; and Beijing Natural Science Foundation [grant numbers 7202138, 7181007].

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Correspondence to Xiao-guang Chen or Sen Zhang.

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Chen, Yy., Chen, Xg. & Zhang, S. Druggability of lipid metabolism modulation against renal fibrosis. Acta Pharmacol Sin (2021). https://doi.org/10.1038/s41401-021-00660-1

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Keywords

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

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