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TLR2 protects cisplatin‐induced acute kidney injury associated with autophagy via PI3K/Akt signaling pathway
Author(s) -
Shen Qing,
Zhang Xi,
Li Qiuying,
Zhang Jing,
Lai Heng,
Gan Hua,
Du Xiaogang,
Li Manli
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27722
Subject(s) - autophagy , pi3k/akt/mtor pathway , protein kinase b , microbiology and biotechnology , cisplatin , acute kidney injury , signal transduction , tlr2 , cancer research , chemistry , medicine , biology , apoptosis , biochemistry , tlr4 , chemotherapy
Abstract Toll‐like receptors (TLRs), which are essential components of the innate immune response, play an important role in acute kidney injury (AKI). Toll‐like receptor 2 (TLR2) is constitutively expressed in tubular epithelial cells of the kidney and participates in cisplatin‐induced AKI. The autophagy is a dynamic catabolic process that maintains intracellular homeostasis, which is involved in the pathogenesis of AKI. Recent studies demonstrate that PI3K/Akt signaling pathway regulates autophagy in response to various stimuli. Therefore, we propose that cisplatin might activate TLR2, which subsequently phosphorylates PI3K/Akt, leading to enhanced autophagy of renal tubular epithelial cells and protecting cisplatin‐induced AKI. We found that TLR2 expression was significantly increased in the kidney after the cisplatin treatment. TLR2‐deficient mice exacerbated renal injury in cisplatin‐induced AKI, with higher serum creatinine and blood urea nitrogen, more severe morphological injury compared with that of wild‐type mice. In vitro, we found that inhibition of TLR2 reduced tubular epithelial cell autophagy after the cisplatin treatment. Mechanistically, TLR2 inhibited autophagy via activating PI3K/Akt signaling pathway in renal tubular epithelial cells after the cisplatin treatment. Take together, these results suggest that TLR2 may protect cisplatin‐induced AKI by activating autophagy via PI3K/Akt signaling pathway.

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