Cargando…

Changes in the Expression of the Toll-Like Receptor System in the Aging Rat Kidneys

BACKGROUND: The mechanisms of kidney aging are not yet clear. Studies have shown that immunological inflammation is related to kidney aging. Toll-like receptors (TLRs) are one of the receptor types of the body's innate immune system. The function of the TLR system and the mechanisms by which it...

Descripción completa

Detalles Bibliográficos
Autores principales: Xi, Yue, Shao, Feng, Bai, Xue-Yuan, Cai, Guangyan, Lv, Yang, Chen, Xiangmei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4014502/
https://www.ncbi.nlm.nih.gov/pubmed/24810370
http://dx.doi.org/10.1371/journal.pone.0096351
_version_ 1782315186487558144
author Xi, Yue
Shao, Feng
Bai, Xue-Yuan
Cai, Guangyan
Lv, Yang
Chen, Xiangmei
author_facet Xi, Yue
Shao, Feng
Bai, Xue-Yuan
Cai, Guangyan
Lv, Yang
Chen, Xiangmei
author_sort Xi, Yue
collection PubMed
description BACKGROUND: The mechanisms of kidney aging are not yet clear. Studies have shown that immunological inflammation is related to kidney aging. Toll-like receptors (TLRs) are one of the receptor types of the body's innate immune system. The function of the TLR system and the mechanisms by which it functions in renal aging remain unclear. In the present study, we, for the first time, systematically investigated the role of the TLR system and the inflammation responses activated by TLRs during kidney aging. METHODS: We used western blot and immunohistochemistry to systematically analyze the changes in the expression and activation of the endogenous TLR ligands HSP70 and HMGB1, the TLRs (TLR1–TLR11), their downstream signaling pathway molecules MyD88 and Phospho-IRF-3, and the NF-κB signaling pathway molecules Phospho-IKKβ, Phospho-IκBα (NF-κB inhibition factor α), NF-κBp65, and Phospho-NF-κBp65 (activated NF-κB p65) in the kidneys of 3 months old (youth group), 12 months old (middle age group), and 24 months old (elderly group) rats. We used RT-qPCR to detect the mRNA expression changes of the proinflammatory cytokines CCL3, CCL4, CCL5, CD80, TNF-α, and IL-12b in the rat renal tissues of the various age groups. RESULTS: We found that during kidney aging, the HSP70 and HMGB1 expression levels were significantly increased, and the expression levels of TLR1, 2, 3, 4, 5, and 11 and their downstream signaling pathway molecules MyD88 and Phospho-IRF-3 were markedly elevated. Further studies have shown that in the aging kidneys, the expression levels of the NF-κB signaling pathway molecules Phospho-IKKβ, Phospho-IκBα, NF-κBp65, and Phospho-NF-κBp65 were obviously increased, and those of the proinflammatory cytokines CCL3, CCL4, CCL5, CD80, TNF-α, and IL-12b were significantly upregulated. CONCLUSIONS: These results showed that the TLR system might play an important role during the kidney aging process maybe by activating the NF-κB signaling pathway and promoting the high expression of inflammation factors.
format Online
Article
Text
id pubmed-4014502
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-40145022014-05-14 Changes in the Expression of the Toll-Like Receptor System in the Aging Rat Kidneys Xi, Yue Shao, Feng Bai, Xue-Yuan Cai, Guangyan Lv, Yang Chen, Xiangmei PLoS One Research Article BACKGROUND: The mechanisms of kidney aging are not yet clear. Studies have shown that immunological inflammation is related to kidney aging. Toll-like receptors (TLRs) are one of the receptor types of the body's innate immune system. The function of the TLR system and the mechanisms by which it functions in renal aging remain unclear. In the present study, we, for the first time, systematically investigated the role of the TLR system and the inflammation responses activated by TLRs during kidney aging. METHODS: We used western blot and immunohistochemistry to systematically analyze the changes in the expression and activation of the endogenous TLR ligands HSP70 and HMGB1, the TLRs (TLR1–TLR11), their downstream signaling pathway molecules MyD88 and Phospho-IRF-3, and the NF-κB signaling pathway molecules Phospho-IKKβ, Phospho-IκBα (NF-κB inhibition factor α), NF-κBp65, and Phospho-NF-κBp65 (activated NF-κB p65) in the kidneys of 3 months old (youth group), 12 months old (middle age group), and 24 months old (elderly group) rats. We used RT-qPCR to detect the mRNA expression changes of the proinflammatory cytokines CCL3, CCL4, CCL5, CD80, TNF-α, and IL-12b in the rat renal tissues of the various age groups. RESULTS: We found that during kidney aging, the HSP70 and HMGB1 expression levels were significantly increased, and the expression levels of TLR1, 2, 3, 4, 5, and 11 and their downstream signaling pathway molecules MyD88 and Phospho-IRF-3 were markedly elevated. Further studies have shown that in the aging kidneys, the expression levels of the NF-κB signaling pathway molecules Phospho-IKKβ, Phospho-IκBα, NF-κBp65, and Phospho-NF-κBp65 were obviously increased, and those of the proinflammatory cytokines CCL3, CCL4, CCL5, CD80, TNF-α, and IL-12b were significantly upregulated. CONCLUSIONS: These results showed that the TLR system might play an important role during the kidney aging process maybe by activating the NF-κB signaling pathway and promoting the high expression of inflammation factors. Public Library of Science 2014-05-08 /pmc/articles/PMC4014502/ /pubmed/24810370 http://dx.doi.org/10.1371/journal.pone.0096351 Text en © 2014 Xi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Xi, Yue
Shao, Feng
Bai, Xue-Yuan
Cai, Guangyan
Lv, Yang
Chen, Xiangmei
Changes in the Expression of the Toll-Like Receptor System in the Aging Rat Kidneys
title Changes in the Expression of the Toll-Like Receptor System in the Aging Rat Kidneys
title_full Changes in the Expression of the Toll-Like Receptor System in the Aging Rat Kidneys
title_fullStr Changes in the Expression of the Toll-Like Receptor System in the Aging Rat Kidneys
title_full_unstemmed Changes in the Expression of the Toll-Like Receptor System in the Aging Rat Kidneys
title_short Changes in the Expression of the Toll-Like Receptor System in the Aging Rat Kidneys
title_sort changes in the expression of the toll-like receptor system in the aging rat kidneys
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4014502/
https://www.ncbi.nlm.nih.gov/pubmed/24810370
http://dx.doi.org/10.1371/journal.pone.0096351
work_keys_str_mv AT xiyue changesintheexpressionofthetolllikereceptorsystemintheagingratkidneys
AT shaofeng changesintheexpressionofthetolllikereceptorsystemintheagingratkidneys
AT baixueyuan changesintheexpressionofthetolllikereceptorsystemintheagingratkidneys
AT caiguangyan changesintheexpressionofthetolllikereceptorsystemintheagingratkidneys
AT lvyang changesintheexpressionofthetolllikereceptorsystemintheagingratkidneys
AT chenxiangmei changesintheexpressionofthetolllikereceptorsystemintheagingratkidneys