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

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

Author information

1
Division of Nephrology, Huadu District People's Hospital of Guangzhou, Southern Medical University, Guangzhou 510800, P.R. China (lihy0726@126.com (fengjx9101@126.com.
2
Division of Nephrology, Huadu District People's Hospital of Guangzhou, Southern Medical University, Guangzhou 510800, P.R. China.
3
Division of Nephrology, Xuhui District Centeral Hospital of Shanghai, Shanghai, P.R. China (lihy0726@126.com (fengjx9101@126.com.

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

PMID:
30455396
PMCID:
PMC6435560
DOI:
10.1042/BSR20181803
[Indexed for MEDLINE]
Free PMC Article

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