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...
Autores principales: | , , , |
---|---|
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 |