PARP1 Deficiency Attenuates Cisplatin Nephrotoxicity and Renal COX-2/PGE2 Response
- 1Interdisciplinary Graduate Program in Advanced Convergence Technology & Science, Jeju National University, Jeju 63243, Republic of Korea
- 2Department of Anatomy, College of Medicine, Jeju National University, Jeju 63243, Republic of Korea
- 3College of Pharmacy, Jeju National University, Jeju 63243, Republic of Korea
Abstract
Cisplatin is a widely used chemotherapeutic agent whose clinical utility is limited by nephrotoxicity, characterized by tubular injury and renal inflammation. Poly(ADP-ribose) polymerase 1 (PARP1) contributes to cisplatin-induced kidney injury and inflammatory signaling, but the downstream inflammatory pathways involved remain incompletely defined. Here, we investigated whether PARP1 modulates the renal cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) response during cisplatin-induced acute kidney injury (AKI). Female wild-type and Parp1-knockout (KO) mice on a C57BL/6 background received a single intraperitoneal injection of cisplatin (20 mg/kg) and were evaluated at days 1 and 4, while male mice were evaluated at day 4 for renal function. Renal function, tubular injury, inflammatory gene expression, NF-κB activation, Ptgs2 mRNA and COX-2 protein expression, and kidney PGE2 levels were assessed. Cisplatin markedly increased plasma creatinine and blood urea nitrogen levels and induced tubular injury in both the renal cortex and outer stripe of the outer medulla, whereas these changes were significantly attenuated in Parp1 KO mice at day 4. At day 4, cisplatin-induced renal expression of Il1b, Il6, Ccl5, Cxcl1, and Cxcl2 was also substantially reduced by Parp1 deficiency. Cisplatin increased renal NF-κB p65 activation, as assessed by the p-p65/t-p65 ratio, in wild-type mice, whereas this response was significantly attenuated in Parp1 KO mice. Consistently, cisplatin increased renal Ptgs2 mRNA expression, COX-2 protein abundance, and PGE2 levels in wild-type mice, whereas all three responses were significantly attenuated in Parp1 KO mice. In particular, the cisplatin-induced increase in renal PGE2 was nearly abolished in the absence of PARP1. These findings demonstrate that PARP1 deficiency attenuates cisplatin-induced renal dysfunction, tubular injury, and inflammatory responses and identify suppression of NF-κB activation and the COX-2/PGE2 response as features of this protective phenotype. The results support a potential PARP1–NF-κB–COX-2/PGE2 signaling axis in cisplatin nephrotoxicity.
Related
- Phosphate Deficiency Attenuates SnRK1 Activity to Modulate the Phosphate Starvation Response in Arabidopsis thaliana
- Deficiency of peripheral serotonin caused by Tph1 abrogation attenuates cerebral malaria severity
- Galectin-1 deficiency attenuates imiquimod-induced psoriasiform skin inflammation and is associated with reduced macrophage recruitment
- TREM-1 deficiency attenuates RIPK3/MLKL-associated epithelial injury in Klebsiella pneumoniae-induced acute lung injury
- The effects of Sishen Pill on improving diarrhea with kidney yang deficiency syndrome: association with gut microbiota, AQP4, and inflammatory response
BibTeX
@article{bhatti2026parp1,
title = {{PARP1 Deficiency Attenuates Cisplatin Nephrotoxicity and Renal COX-2/PGE2 Response}},
author = {Theophilus Bhatti and Jia-Bin Yu and Ji-Yeong Bae and Jinu Kim},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15191810},
url = {https://europepmc.org/article/PMC/PMC13664194},
note = {CC BY},
}
RIS
TY - JOUR
TI - PARP1 Deficiency Attenuates Cisplatin Nephrotoxicity and Renal COX-2/PGE2 Response
AU - Theophilus Bhatti
AU - Jia-Bin Yu
AU - Ji-Yeong Bae
AU - Jinu Kim
PY - 2026
DA - 2026/10/01
JO - Cells
DO - 10.3390/cells15191810
UR - https://europepmc.org/article/PMC/PMC13664194
AB - Cisplatin is a widely used chemotherapeutic agent whose clinical utility is limited by nephrotoxicity, characterized by tubular injury and renal inflammation. Poly(ADP-ribose) polymerase 1 (PARP1) contributes to cisplatin-induced kidney injury and inflammatory signaling, but the downstream inflammatory pathways involved remain incompletely defined. Here, we investigated whether PARP1 modulates the renal cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) response during cisplatin-induced acute kidney injury (AKI). Female wild-type and Parp1-knockout (KO) mice on a C57BL/6 background received a single intraperitoneal injection of cisplatin (20 mg/kg) and were evaluated at days 1 and 4, while male mice were evaluated at day 4 for renal function. Renal function, tubular injury, inflammatory gene expression, NF-κB activation, Ptgs2 mRNA and COX-2 protein expression, and kidney PGE2 levels were assessed. Cisplatin markedly increased plasma creatinine and blood urea nitrogen levels and induced tubular injury in both the renal cortex and outer stripe of the outer medulla, whereas these changes were significantly attenuated in Parp1 KO mice at day 4. At day 4, cisplatin-induced renal expression of Il1b, Il6, Ccl5, Cxcl1, and Cxcl2 was also substantially reduced by Parp1 deficiency. Cisplatin increased renal NF-κB p65 activation, as assessed by the p-p65/t-p65 ratio, in wild-type mice, whereas this response was significantly attenuated in Parp1 KO mice. Consistently, cisplatin increased renal Ptgs2 mRNA expression, COX-2 protein abundance, and PGE2 levels in wild-type mice, whereas all three responses were significantly attenuated in Parp1 KO mice. In particular, the cisplatin-induced increase in renal PGE2 was nearly abolished in the absence of PARP1. These findings demonstrate that PARP1 deficiency attenuates cisplatin-induced renal dysfunction, tubular injury, and inflammatory responses and identify suppression of NF-κB activation and the COX-2/PGE2 response as features of this protective phenotype. The results support a potential PARP1–NF-κB–COX-2/PGE2 signaling axis in cisplatin nephrotoxicity.
SN - 2073-4409
ER -