TLR2 protects cisplatin-induced acute kidney injury associated with autophagy via PI3K/Akt signaling pathway

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.