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Modeling Hypoxia/Reoxygenation Injury in Proximal Tubular Epithelial Cells
Published on: November 21, 2025
Serum Response Factor Regulates CCN1 to Exacerbate Acute Kidney Injury Through Facilitation of Ferroptosis-Related
Yanfei Wang1, Chen Guan1, Chenyu Li1
1Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Aim:
To explore the regulation and function of serum response factor (SRF)/Cellular communication network factor 1 (CCN1) pathway in ferroptosis in ischemia/reperfusion (I/R) acute kidney injury (AKI).
Methods:
The level of SRF, CCN1, ferroptosis markers (TFR1, ACSL4, xCT, GPX4), ROS and SOD were examined in HK-2 cells under hypoxia/reoxygenation (H/R) treatment or rat renal tissue samples after I/R treatment. SRF was overexpressed by pcDNA-SRF plasmid and suppressed by CCG-1423 (a small molecule inhibitor of SRF) or SRF siRNA to study how SRF influences ferroptosis through CCN1 in I/R AKI.
Results:
In HK-2 cells under H/R treatment and renal tissue from I/R rats, the SRF along with CCN1, TFR1 and ACSL4 expression was upregulated, while xCT and GPX4 expression was downregulated. SRF upregulation in HK-2 cells increased CCN1 expression and was associated with ferroptosis-related changes. Blockade of SRF by CCG-1423 or an SRF-specific siRNA reduced CCN1 induction, protected renal tubular epithelial cells from ferroptosis-related injury, and alleviated I/R AKI both in vitro and in vivo.
Conclusion:
Increased SRF/CCN1 pathway activity may be associated with ferroptosis-related injury and dysfunction in renal tubular epithelial cells during AKI. Targeting SRF with CCG-1423 may represent a potential therapeutic strategy of AKI.
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