Image_1_Poly (ADP-Ribose) Polymerase Inhibitor Treatment as a Novel Therapy Attenuating Renal Ischemia-Reperfusion Injury.pdf (1.74 MB)

Image_1_Poly (ADP-Ribose) Polymerase Inhibitor Treatment as a Novel Therapy Attenuating Renal Ischemia-Reperfusion Injury.pdf

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posted on 16.10.2020, 13:25 by Hye Ryoun Jang, Kyungho Lee, Junseok Jeon, Jung-Ryul Kim, Jung Eun Lee, Ghee Young Kwon, Yoon-Goo Kim, Dae Joong Kim, Jae-Wook Ko, Wooseong Huh

Intrarenal robust inflammatory response following ischemia-reperfusion injury (IRI) is a major factor in the pathogenesis of renal injury in ischemic acute kidney injury (AKI). Although numerous studies have investigated various agents of immune modulation or suppression for ischemic AKI, few showed reproducible effects. We hypothesized that poly (ADP-ribose) polymerase (PARP) inhibitor may favorably change post-ischemic intrarenal immunologic micromilieu by reducing damage-associated molecular pattern (DAMP) signals and improve renal outcome in ischemic AKI. The effects of JPI-289 (a PARP inhibitor) on early renal injury in a murine IRI model and hypoxic HK-2 cell model were investigated. Bilateral IRI surgery was performed in three groups of 9-week-old male C57BL/6 mice (control, JPI-289 50 mg/kg, and JPI-289 100 mg/kg; n = 9–10 in each group). Saline or JPI-289 was intraperitoneally injected. Renal function deterioration was significantly attenuated in the JPI-289 treatment groups in a dose-dependent manner. Inflammatory cell infiltration and proinflammatory cytokine/chemokine expressions in the post-ischemic kidneys were also attenuated by JPI-289 treatment. JPI-289 treatment at 0.5 and 0.75 μg/ml facilitated the proliferation of hypoxic HK-2 cells. PARP inhibition with JPI-289 treatment showed favorable effects in ischemic AKI by attenuating intrarenal inflammatory cascade in a murine model and facilitating proliferation of hypoxic HK-2 cells.

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