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Tubular-specific ablation of Tiki2 exacerbates inflammation in ischemia/reperfusion-induced acute kidney injury by derepressing Wnt5a/Ror signaling

GSE293486 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/04/08 Platform GPL24247
Summary
Ischemia/reperfusion-induced acute kidney injury (AKI) occurs in several clinical conditions accompanied by inflammation, but the underlying mechanisms remain elusive. The Wnt inhibitor Tiki2 is highly expressed in the kidney with unknown function. Here, we demonstrated that Tiki2 is highly expressed in proximal tubular epithelial cells (PTECs) and is dynamically regulated in AKI. Tubular epithelial cell-specific ablation of Tiki2 aggravated immune cell infiltration and tubular injury in IR-induced AKI. Mechanistically, Tiki2 ablation increased the activity of Wnt5a/Ror signaling, which is activated in PTECs in IR-induced AKI, leading to increased active JNK/ERK signaling and the secretion of chemokines and cytokines to promote the infiltration of immune cells. Furthermore, the increased severity of injury and inflammation caused by Tiki2 ablation could be relieved by knocking down Ror2 in PTECs. Our study reveals the critical roles of Wnt5a/Ror signaling and its negative regulator Tiki2 in IR-induced AKI, which are potential therapeutic targets for treating AKI
Published in
Tiki2 restrains Wnt5a/Ror signaling to limit inflammation in acute kidney injury
Yang C, Wang S, Zhang M et al. · Communications biology 2026 · PMID 41981279 · doi:10.1038/s42003-026-10053-x
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Also filed as BioProject PRJNA1242021 and SRA study SRP573122. Searching any of these in the dataset finder brings you back here.

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