Reduced kidney levels of lysophosphatidic acids in rats after chronic administration of aristolochic acid: Its possible protective role in renal fibrosis

Aristolochic acid (AA) is considered to be a causative agent for progressive interstitial renal fibrosis, leading to AA nephropathy. Lysophosphatidic acid (LPA) is a mediator in the onset of renal fibrosis. In this study, we analyzed the molecular species of LPA and its precursor lysophospholipids i...

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Autores principales: Tsutsumi, Toshihiko, Yamakawa, Syougo, Ishihara, Akira, Yamamoto, Aimi, Tanaka, Tamotsu, Tokumura, Akira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2015
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598376/
https://www.ncbi.nlm.nih.gov/pubmed/28962344
http://dx.doi.org/10.1016/j.toxrep.2015.02.012
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author Tsutsumi, Toshihiko
Yamakawa, Syougo
Ishihara, Akira
Yamamoto, Aimi
Tanaka, Tamotsu
Tokumura, Akira
author_facet Tsutsumi, Toshihiko
Yamakawa, Syougo
Ishihara, Akira
Yamamoto, Aimi
Tanaka, Tamotsu
Tokumura, Akira
author_sort Tsutsumi, Toshihiko
collection PubMed
description Aristolochic acid (AA) is considered to be a causative agent for progressive interstitial renal fibrosis, leading to AA nephropathy. Lysophosphatidic acid (LPA) is a mediator in the onset of renal fibrosis. In this study, we analyzed the molecular species of LPA and its precursor lysophospholipids in kidney tissue from rats exposed to AA. Daily intraperitoneal injections of AA for 35 days to rats gave rise to fibrosis in kidney, decreased the kidney levels of LPA, lysophosphatidylserine and lysophosphatidylinositol. In rat renal cell lines (NRK52E and NRK49F), AA-induced cytotoxicity was potentiated by Ki16425, LPA(1,3) receptor antagonist. The level of mRNA encording α-smooth muscle actin was significantly increased by AA-treatment only in NRK52E cells, while the mRNA level of collagen III was decreased in both NRK52E and NRK49F cells. These results suggest that endogenous LPA in rat kidney prevents AA-induced renal fibrosis.
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spelling pubmed-55983762017-09-28 Reduced kidney levels of lysophosphatidic acids in rats after chronic administration of aristolochic acid: Its possible protective role in renal fibrosis Tsutsumi, Toshihiko Yamakawa, Syougo Ishihara, Akira Yamamoto, Aimi Tanaka, Tamotsu Tokumura, Akira Toxicol Rep Article Aristolochic acid (AA) is considered to be a causative agent for progressive interstitial renal fibrosis, leading to AA nephropathy. Lysophosphatidic acid (LPA) is a mediator in the onset of renal fibrosis. In this study, we analyzed the molecular species of LPA and its precursor lysophospholipids in kidney tissue from rats exposed to AA. Daily intraperitoneal injections of AA for 35 days to rats gave rise to fibrosis in kidney, decreased the kidney levels of LPA, lysophosphatidylserine and lysophosphatidylinositol. In rat renal cell lines (NRK52E and NRK49F), AA-induced cytotoxicity was potentiated by Ki16425, LPA(1,3) receptor antagonist. The level of mRNA encording α-smooth muscle actin was significantly increased by AA-treatment only in NRK52E cells, while the mRNA level of collagen III was decreased in both NRK52E and NRK49F cells. These results suggest that endogenous LPA in rat kidney prevents AA-induced renal fibrosis. Elsevier 2015-02-28 /pmc/articles/PMC5598376/ /pubmed/28962344 http://dx.doi.org/10.1016/j.toxrep.2015.02.012 Text en © 2015 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Tsutsumi, Toshihiko
Yamakawa, Syougo
Ishihara, Akira
Yamamoto, Aimi
Tanaka, Tamotsu
Tokumura, Akira
Reduced kidney levels of lysophosphatidic acids in rats after chronic administration of aristolochic acid: Its possible protective role in renal fibrosis
title Reduced kidney levels of lysophosphatidic acids in rats after chronic administration of aristolochic acid: Its possible protective role in renal fibrosis
title_full Reduced kidney levels of lysophosphatidic acids in rats after chronic administration of aristolochic acid: Its possible protective role in renal fibrosis
title_fullStr Reduced kidney levels of lysophosphatidic acids in rats after chronic administration of aristolochic acid: Its possible protective role in renal fibrosis
title_full_unstemmed Reduced kidney levels of lysophosphatidic acids in rats after chronic administration of aristolochic acid: Its possible protective role in renal fibrosis
title_short Reduced kidney levels of lysophosphatidic acids in rats after chronic administration of aristolochic acid: Its possible protective role in renal fibrosis
title_sort reduced kidney levels of lysophosphatidic acids in rats after chronic administration of aristolochic acid: its possible protective role in renal fibrosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598376/
https://www.ncbi.nlm.nih.gov/pubmed/28962344
http://dx.doi.org/10.1016/j.toxrep.2015.02.012
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