Abstract: FR-PO0185
RUNX1 Deficiency Suppresses Tubular Injury and Kidney Fibrosis via Reduction of Endoplasmic Reticulum Stress
Session Information
- AKI: Mechanisms - 2
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Yano-Sakamoto, Keiko, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan
- Kitai, Yuichiro, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan
- Toriu, Naoya, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan
- Yamamoto, Shinya, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan
- Yanagita, Motoko, Kyoto Daigaku Daigakuin Igaku Kenkyuka Igakubu, Kyoto, Kyoto Prefecture, Japan
Background
The runt-related transcription factor (RUNX) family, including RUNX1, RUNX2, and RUNX3, as well as their transcription co-factor core-binding factor beta (CBFβ), are key regulators of diverse biological processes. We previously reported that RUNX1 is expressed in the ureteric bud tip during development. While RUNX1 was absent in any nephron segment in adult mice under physiological conditions, we found that RUNX1 was reactivated in the injured proximal tubules (PTs) after ischemia-reperfusion injury (IRI), and subsequently investigated the role of RUNX1 and CBFβ during IRI.
Methods
RUNX family protein expression was assessed in the kidneys of C57BL/6J mice following IRI. We analyzed PT-specific Runx1 knockout (KO) mice and Cbfb KO mice 4 and 28 days after IRI. The underlying mechanism was explored using photo-isolation chemistry RNA-sequencing (PIC RNA-seq) analysis, which enabled the detection of transcriptome profiles in photo-irradiated areas and in vitro studies.
Results
RUNX1 protein was strongly expressed in injured PTs, whereas RUNX2 and RUNX3 proteins were not expressed. CBFβ protein expression in PT cells was upregulated after IRI, with nuclear localization in some PTs. PT-specific Runx1 KO mice showed decreased tubular injury, cell death, and fibrosis compared with control mice. Moreover, PT-specific Cbfb KO mice exhibited reduced RUNX1 protein expression in injured PTs, and a phenotype similar to that of Runx1 KO mice. PIC RNA-seq analysis of PTs revealed reduced expression of genes involved in protein synthesis, such as ribosome biogenesis and translation, and endoplasmic reticulum (ER) stress-responsive genes in Runx1 KO mice. Consistent with the RNA-seq results, in vitro studies revealed decreased nascent protein synthesis in RUNX1 KO cells. Upon tunicamycin treatment, RUNX1 KO cells showed attenuated cell death and reduced expression of C/EBP homologous protein (CHOP), which is critical for ER stress-induced cell death.
Conclusion
We presented a novel mechanism by which RUNX1/CBFβ signaling promotes tubular injury and fibrosis by enhancing ER stress. Our findings suggest that RUNX1/CBFβ and its downstream pathway represent potential therapeutic targets for mitigating IRI and preventing its progression to chronic kidney disease.