Effects of poly (ADP-ribose) polymerase inhibitor treatment on the repair process of ischemic acute kidney injury

• Published in: Scientific reports Vol. 14; no. 1; p. 159
• Main Authors: Jeon, Junseok, Lee, Kyungho, Jang, Hye Ryoun, Yang, Kyeong Eun, Lee, Cheol-Jung, Ahn, Hyeonju, Park, Woong-Yang, Lee, Jung Eun, Kwon, Ghee Young, Kim, Yoon-Goo, Huh, Wooseong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.01.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 692/4022/1585/4; 692/420/256; Acute Kidney Injury - drug therapy; Acute Kidney Injury - etiology; Acute Kidney Injury - pathology; Animals; Atrophy; Atrophy - pathology; Cell proliferation; Chemokines; Endothelial cells; Endothelial Cells - metabolism; Fibrosis; Humanities and Social Sciences; Hypoxia; Immune system; Inflammation; Ischemia; Ischemia - pathology; Kidney - metabolism; Kidneys; Male; Mice; Mice, Inbred C57BL; multidisciplinary; Phenotypes; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) polymerase; Poly(ADP-ribose) Polymerase Inhibitors - pharmacology; Poly(ADP-ribose) Polymerase Inhibitors - therapeutic use; Poly(ADP-ribose) Polymerases - metabolism; Proximal tubules; Renal function; Reperfusion; Reperfusion Injury - metabolism; Ribose; Science; Science (multidisciplinary); Toll-like receptors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-50630-2

Excessive activation of poly (ADP-ribose) polymerase (PARP) contributes to ischemic acute kidney injury (AKI). PARP inhibition has been shown to be beneficial in renal ischemia–reperfusion injury (IRI) in the early phase, but its role in the repair process remains unclear. The effects of JPI-289, a novel PARP inhibitor, during the healing phase after renal IRI were investigated. IRI was performed on 9-week-old male C57BL/6 mice. Saline or JPI-289 100 mg/kg was intraperitoneally administered once at 24 h or additionally at 48 h after IRI. Hypoxic HK-2 cells were treated with JPI-289. Renal function and fibrosis extent were comparable between groups. JPI-289 treatment caused more prominent tubular atrophy and proinflammatory intrarenal leukocyte phenotypes and cytokines/chemokines changes at 12 weeks after unilateral IRI. JPI-289 treatment enhanced gene expressions associated with collagen formation, toll-like receptors, and the immune system in proximal tubules and endothelial cells after IRI. JPI-289 treatment at 3 or 6 h after hypoxia facilitated proliferation of hypoxic HK-2 cells, whereas further treatment after 24 h suppressed proliferation. Delayed inhibition of PARP after renal IRI did not facilitate the repair process during the early healing phase but rather may aggravate renal tubular atrophy during the late healing phase in ischemic AKI.