Galectin 3 inhibition attenuates renal injury progression in cisplatin-induced nephrotoxicity

Biosci Rep. 2018 Dec 18;38(6):BSR20181803. doi: 10.1042/BSR20181803. Print 2018 Dec 21.

Abstract

Nephrotoxicity is a major toxic effect in chemotherapy, which constitutes up to 60% of hospitalized acute kidney injury (AKI). Very few treatment options exist to slow the transition from AKI to subsequent chronic kidney diseases (CKD). Here, we demonstrate that galectin-3 (Gal-3), a β-galactoside binding lectin that plays an important role in kidney fibrosis and renal failure, is one of the key factors for renal injury progression. Ectopic overexpression of Gal-3 significantly decreased the viability of HEK293, simultaneously inducing of cell cycle arrest and apoptosis. However, inhibition of Gal-3, mediated by modified citrus pectin (MCP), predominantly antagonized the pro-apoptotic effects. Mice were pre-treated with normal or 1% MCP-supplemented drinking water 1 week before cisplatin injection. Analyses of serum creatinine and renal tissue damage indicated that MCP-treated mice demonstrated increased renal function and attenuated renal fibrosis after cisplatin-induced injury. MCP-treated mice also demonstrated decreased renal fibrosis and apoptosis, as revealed by masson trichrome staining and Western blot analysis of cleaved caspase-3. Additionally, the protective role of Gal-3 inhibition in the kidney injury was shown to be mediated by protein kinase C α (PKC-α), which promoted cell apoptosis and collagen I synthesis in HEK293 cells. These results demonstrated the potential Gal-3 and PKC-α as therapeutic targets for the treatment of AKI and CKD.

Keywords: acute kidney injury; apoptosis; galectin-3; modified citrus pectin; renal fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / blood
  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / genetics*
  • Acute Kidney Injury / pathology
  • Animals
  • Apoptosis / genetics
  • Caspase 3 / genetics
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects*
  • Creatinine / blood
  • Disease Models, Animal
  • Fibrosis / blood
  • Fibrosis / chemically induced
  • Fibrosis / genetics*
  • Fibrosis / pathology
  • Galectin 3 / antagonists & inhibitors
  • Galectin 3 / genetics*
  • Gene Expression Regulation
  • Humans
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Mice
  • Neoplasms / complications
  • Neoplasms / drug therapy
  • Pectins / genetics
  • Protein Kinase C-alpha / genetics*
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / genetics
  • Renal Insufficiency, Chronic / pathology

Substances

  • Galectin 3
  • LGALS3 protein, human
  • citrus pectin
  • Pectins
  • Creatinine
  • Protein Kinase C-alpha
  • Caspase 3
  • Cisplatin