Kidney Week

Abstract: FR-PO0223

BACH1 Modulates Oxidative Stress Response in Kidney Cells Influencing Tubular Cell Survival

Session Information

• CKD: Mechanisms of Injury and Fibrosis - 2
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2203 CKD (Non-Dialysis): Mechanisms

Authors

• Carracedo, Miguel, AstraZeneca R&D Gothenburg, Mölndal, Västra Götaland County, Sweden

Miguel Carracedo, PhD

• Tati, Ramesh, AstraZeneca R&D Gothenburg, Mölndal, Västra Götaland County, Sweden

Ramesh Tati, PhD

• Cederblad, Linda, AstraZeneca R&D Gothenburg, Mölndal, Västra Götaland County, Sweden

Linda Cederblad

• Rosengren, Birgitta E., AstraZeneca R&D Gothenburg, Mölndal, Västra Götaland County, Sweden

Birgitta E. Rosengren

• Wennberg Huldt, Charlotte, AstraZeneca R&D Gothenburg, Mölndal, Västra Götaland County, Sweden

Charlotte Wennberg Huldt, PhD

• Bilkei-Gorzo, Orsolya, AstraZeneca R&D Gothenburg, Mölndal, Västra Götaland County, Sweden

Orsolya Bilkei-Gorzo

• Holmgren, Gustav, AstraZeneca R&D Gothenburg, Mölndal, Västra Götaland County, Sweden

Gustav Holmgren, MSc, PhD

• Chandrasekar, Vijay, AstraZeneca R&D Gothenburg, Mölndal, Västra Götaland County, Sweden

Vijay Chandrasekar, PhD

• Lal, Mark, AstraZeneca R&D Gothenburg, Mölndal, Västra Götaland County, Sweden

Mark Lal, PhD

Background

Chronic and acute kidney injury are amplified by excessive reactive oxygen species (ROS), driving cellular damage, inflammation, and fibrosis that accelerate loss of renal function. BACH1 (BTB and CNC Homology 1) is a transcription factor involved in regulating oxidative stress and cellular processes, however, its role in kidney cells and oxidative injury remains undefined.

Methods

We investigated BACH1-dependent regulation of antioxidant pathways in renal cells using CRISPR knockouts and overexpression approaches. We compared responses in tubular epithelial versus endothelial cells, quantified cell viability and activation after tert butyl hydroperoxide (tBHP) exposure and performed proteomics in BACH1 knockout (KO) tubular cells to define pathway-level changes.

Results

BACH1 KO in tubular cells showed increased HMOX1 upregulation compared to endothelial cells, suggesting cell type–specific BACH1 control of redox homeostasis within the kidney. Unbiased proteomics in BACH1 KO tubular cells demonstrated broad upregulation of antioxidant pathways and heme metabolism, consistent with derepression of NRF2/HMOX1 circuitry. Functionally, BACH1 KO protected tubular cells from tBHP-induced cell death, supporting a pro-survival phenotype under oxidant challenge. BACH1 KO cells exhibited a synergistic increase in HMOX1 upon KEAP1 inhibition, indicating BACH1 acts as a negative regulator of stress-inducible cytoprotective programs. Conversely, BACH1 overexpression blunted HMOX1 upregulation by KEAP1 inhibition, an effect magnified under oxidative stress.

Conclusion

BACH1 acts as a critical brake for NRF2 antioxidant responsiveness in renal cells. Its deletion enhances antioxidant and heme metabolic programs and confers oxidant tolerance in tubular epithelium, with more pronounced effects than in the endothelium. These findings position BACH1 as a potential therapeutic target to mitigate ROS-driven injury in AKI and CKD by relieving repression of endogenous cytoprotective pathways. Future studies should test BACH1 inhibition in vivo and map cell type specific mechanisms to inform redox guided interventions in kidney disease.

Funding

• Commercial Support – AstraZeneca