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ABSTRACT: 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-?B signaling pathway molecules Phospho-IKK?, Phospho-I?B? (NF-?B inhibition factor ?), NF-?Bp65, and Phospho-NF-?Bp65 (activated NF-?B 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-?, 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-?B signaling pathway molecules Phospho-IKK?, Phospho-I?B?, NF-?Bp65, and Phospho-NF-?Bp65 were obviously increased, and those of the proinflammatory cytokines CCL3, CCL4, CCL5, CD80, TNF-?, 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-?B signaling pathway and promoting the high expression of inflammation factors.
SUBMITTER: Xi Y
PROVIDER: S-EPMC4014502 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
Xi Yue Y Shao Feng F Bai Xue-Yuan XY Cai Guangyan G Lv Yang Y Chen Xiangmei X
PloS one 20140508 5
<h4>Background</h4>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 ...[more]