Abstract
Classically activated macrophages contribute to the development of renal ischemia-reperfusion injury (IRI). This study aimed to investigate the role of transient receptor potential ankyrin 1 (Trpa1), a regulator of macrophage activation, in IRI-induced acute kidney injury (AKI) by using the Trpa1 gene knockout (Trpa1-/-) mouse model. Male 8-week-old Trpa1-/- mice and wild-type (WT) littermates were subjected to renal ischemia for 35 minutes by clamping bilateral renal pedicles under isoflurane anesthesia, and blood and tissue samples were collected 24 hours after reperfusion and analyzed with histological and molecular measurements. Following IRI, Trpa1-/- mice developed more deteriorated biochemical and morphological signs of AKI when comparing with WT mice. More classically activated M1 macrophages were found in the kidneys of Trpa1-/- mice comparing with WT mice after IRI, while the counts of alternatively activated M2 macrophages in the kidney were similar between the 2 strains after IRI. Furthermore, significantly higher expression levels of proinflammatory markers including interleukin-1 beta and tumor necrosis factor alpha were detected in the kidney of Trpa1-/- mice compared with WT mice after IRI. The levels of TRPA1 protein in the kidney of WT mice were also decreased after IRI. Our results show that ablation of Trpa1 exacerbates infiltration of classically activated macrophages, renal inflammation, and renal injury in mice after IRI. These findings suggest that activation of TRPA1 may protect against IRI-induced AKI via regulation of macrophage-mediated inflammatory pathway.
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