Therapeutic potential for renal fibrosis by targeting Smad3-dependent noncoding RNAs

Mol Ther. 2024 Feb 7;32(2):313-324. doi: 10.1016/j.ymthe.2023.12.009. Epub 2023 Dec 12.

Abstract

Renal fibrosis is a characteristic hallmark of chronic kidney disease (CKD) that ultimately results in renal failure, leaving patients with few therapeutic options. TGF-β is a master regulator of renal fibrosis and mediates progressive renal fibrosis via both canonical and noncanonical signaling pathways. In the canonical Smad signaling, Smad3 is a key mediator in tissue fibrosis and mediates renal fibrosis via a number of noncoding RNAs (ncRNAs). In this regard, targeting Smad3-dependent ncRNAs may offer a specific therapy for renal fibrosis. This review highlights the significance and innovation of TGF-β/Smad3-associated ncRNAs as biomarkers and therapeutic targets in renal fibrogenesis. In addition, the underlying mechanisms of these ncRNAs and their future perspectives in the treatment of renal fibrosis are discussed.

Keywords: Smad3; TGF-β; noncoding RNAs; renal fibrosis; therapy.

Publication types

  • Review

MeSH terms

  • Fibrosis
  • Humans
  • Kidney* / metabolism
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism
  • Renal Insufficiency, Chronic* / genetics
  • Renal Insufficiency, Chronic* / metabolism
  • Renal Insufficiency, Chronic* / therapy
  • Smad3 Protein / genetics
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism

Substances

  • RNA, Untranslated
  • Smad3 Protein
  • Transforming Growth Factor beta
  • SMAD3 protein, human