Multi-omics analysis identifies S100a10/Anxa2 complex within proximal tubule aggravates acute kidney injury through p-Stat3/Spp1 signaling.

BACKGROUND

Acute kidney injury (AKI) has become a global public health problem that seriously endangers human health, the treatment for AKI is mainly supportive and there is no targeted, efficient and low-toxicity treatment.

METHODS &

RESULTS

Multi-omics including bulk RNA-seq, scRNA-seq, spatial transcriptomics were used to find the high differential expressed genes between con and AKI. While S100a10 was consistently found to be significantly increased in renal tubular epithelial cells after cisplatin and IRI induced AKI compared with normal control. As S100a10 mainly interacts with Anxa2 to form a tetramer complex. The complex inhibitor, A2ti, was found to improve cisplatin and IRI induced AKI, the mechanisms was uncovered by RNA-seq and ChIP-seq data, which shows A2ti may inhibit the p-Stat3/Spp1 signaling, while colivelin, a Stat3 activator, can reverse the protective role of A2ti. In order to further confirm the role of S100a10 within proximal tubule (PT), rAAV-SGLT2-EGFP-shS100a10 virus was used to knock down s100a10 within PT through tail vein injection, and down-regulation of S100a10 can partially improve cisplatin induced AKI through p-Stat3/Spp1 signaling.

CONCLUSION

It has been consistently found that the S100a10-Anxa2 complex is involved in AKI by regulating p-Stat3/Spp1 through multi-omics analysis and experiment validation.