Cargando…

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

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 b...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Hong-yan, Yang, Shen, Li, Jing-chun, Feng, Jian-xun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435560/
https://www.ncbi.nlm.nih.gov/pubmed/30455396
http://dx.doi.org/10.1042/BSR20181803
_version_ 1783406658440921088
author Li, Hong-yan
Yang, Shen
Li, Jing-chun
Feng, Jian-xun
author_facet Li, Hong-yan
Yang, Shen
Li, Jing-chun
Feng, Jian-xun
author_sort Li, Hong-yan
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6435560
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Portland Press Ltd.
record_format MEDLINE/PubMed
spelling pubmed-64355602019-04-12 Galectin 3 inhibition attenuates renal injury progression in cisplatin-induced nephrotoxicity Li, Hong-yan Yang, Shen Li, Jing-chun Feng, Jian-xun Biosci Rep Research Articles 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. Portland Press Ltd. 2018-12-18 /pmc/articles/PMC6435560/ /pubmed/30455396 http://dx.doi.org/10.1042/BSR20181803 Text en © 2018 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
Li, Hong-yan
Yang, Shen
Li, Jing-chun
Feng, Jian-xun
Galectin 3 inhibition attenuates renal injury progression in cisplatin-induced nephrotoxicity
title Galectin 3 inhibition attenuates renal injury progression in cisplatin-induced nephrotoxicity
title_full Galectin 3 inhibition attenuates renal injury progression in cisplatin-induced nephrotoxicity
title_fullStr Galectin 3 inhibition attenuates renal injury progression in cisplatin-induced nephrotoxicity
title_full_unstemmed Galectin 3 inhibition attenuates renal injury progression in cisplatin-induced nephrotoxicity
title_short Galectin 3 inhibition attenuates renal injury progression in cisplatin-induced nephrotoxicity
title_sort galectin 3 inhibition attenuates renal injury progression in cisplatin-induced nephrotoxicity
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435560/
https://www.ncbi.nlm.nih.gov/pubmed/30455396
http://dx.doi.org/10.1042/BSR20181803
work_keys_str_mv AT lihongyan galectin3inhibitionattenuatesrenalinjuryprogressionincisplatininducednephrotoxicity
AT yangshen galectin3inhibitionattenuatesrenalinjuryprogressionincisplatininducednephrotoxicity
AT lijingchun galectin3inhibitionattenuatesrenalinjuryprogressionincisplatininducednephrotoxicity
AT fengjianxun galectin3inhibitionattenuatesrenalinjuryprogressionincisplatininducednephrotoxicity