Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 19;53(1):119.
doi: 10.1007/s00240-025-01793-2.

CDKN1A attenuates ferroptosis in renal tubular epithelial cells and alleviates calcium oxalate crystal deposition under hyperoxaluric conditions

Chujiang He  1 , Zijie Xu  1 , Chaoliang Xu  2 , Minglei Sha  3 , Yi Shao  4
Affiliations

CDKN1A attenuates ferroptosis in renal tubular epithelial cells and alleviates calcium oxalate crystal deposition under hyperoxaluric conditions

Chujiang He et al. Urolithiasis. .

Abstract

Hyperoxaluria is a recognized risk factor for calcium oxalate nephrolithiasis, often contributing to tubular injury and crystal deposition. This study aimed to investigate the involvement of ferroptosis in hyperoxaluria-induced renal damage and identify key regulatory genes with therapeutic relevance. In vivo and in vitro hyperoxaluria models were established, and ferroptosis-related differentially expressed genes (FRDEGs) were screened via GEO and FerrDb databases. Functional enrichment analyses were conducted using GO and KEGG. CDKN1A was identified as a hub gene through PPI network analysis and subsequently validated in both in vivo and in vitro hyperoxaluria models via RT-qPCR and Western blotting. Concurrently, activation of ferroptosis was observed under hyperoxaluric conditions in both models, as indicated by changes in key ferroptosis markers. In HK-2 cells, CDKN1A expression decreased upon Erastin exposure, and its knockdown enhanced ferroptosis sensitivity, confirming its potential suppressive role. Additionally, analysis of the human dataset GSE73680 revealed a significant upregulation of CDKN1A expression in Randall's plaques from calcium oxalate stone patients and enrichment of ferroptosis-related pathways, consistent with findings from the mouse dataset, supporting its relevance in crystal-associated pathology. Furthermore, candidate compounds potentially activating CDKN1A were predicted based on GTEx-derived expression profiles. These findings suggest that ferroptosis contributes to hyperoxaluria-associated renal epithelial injury and crystal deposition. CDKN1A may exert a protective role by modulating ferroptosis, providing mechanistic insight into oxalate-induced kidney injury and offering a basis for developing strategies to mitigate the risk of calcium oxalate stone formation.

Keywords: CDKN1A; Calcium oxalate crystal deposition; Ferroptosis; Hyperoxaluria.

PubMed Disclaimer

Conflict of interest statement

Declarations. Competing interests: The authors declare that they hold no financial or personal relationships with any institutions or organizations that could inappropriately influence or bias the content presented in this manuscript.

References

    1. Teichman JM (2004) Clinical practice. Acute renal colic from ureteral calculus. N Engl J Med 350:684–693. https://doi.org/10.1056/NEJMcp030813 - DOI - PubMed
    1. Singh P, Enders FT, Vaughan LE, Bergstralh EJ, Knoedler JJ, Krambeck AE, Lieske JC Rule AD(2015)Stone composition among First-Time symptomatic kidney stone formers in the community. Mayo Clin Proc 90: 1356–1365. https://doi.org/10.1016/j.mayocp.2015.07.016
    1. Coe FL, Worcester EM, Evan AP(2016)Idiopathic hypercalciuria and formation of calcium renal stones. Nat Rev Nephrol 12: 519–533. https://doi.org/10.1038/nrneph.2016.101
    1. Geraghty R, Wood K, Sayer JA(2020)Calcium oxalate crystal deposition in the kidney: identification, causes and consequences. Urolithiasis 48: 377–384. https://doi.org/10.1007/s00240-020-01202-w
    1. Hoppe B (2012) An update on primary hyperoxaluria. Nat Rev Nephrol 8:467–475. https://doi.org/10.1038/nrneph.2012.113 - DOI - PubMed

MeSH terms

Supplementary concepts

LinkOut - more resources