Sirtuin 7 Deficiency Ameliorates Cisplatin-induced Acute Kidney Injury Through Regulation of the Inflammatory Response.

Abstract

Cisplatin-induced acute kidney injury (AKI) has been recognized as one of cisplatin's serious side effects, limiting its use in cancer therapy. Sirtuin 1 (SIRT1) and SIRT3 play protective roles against cisplatin-induced kidney injury. However, the role of SIRT7 in cisplatin-induced kidney injury is not yet known. In this study, we found that Sirt7 knockout (KO) mice were resistant to cisplatin-induced AKI. Furthermore, our studies identified that loss of SIRT7 decreases the expression of tumor necrosis factor-α (TNF-α) by regulating the nuclear expression of the transcription factor nuclear factor kappa B. It has been reported that cisplatin-induced nephrotoxicity is mediated by TNF-α. Our results indicate that SIRT7 plays an important role in cisplatin-induced AKI and suggest the possibility of SIRT7 as a novel therapeutic target for cisplatin-induced nephrotoxicity.

• Authors: Yoshikazu Miyasato, Tatsuya Yoshizawa, Yoshifumi Sato, Terumasa Nakagawa, Yuko Miyasato, Yutaka Kakizoe, Takashige Kuwabara, Masataka Adachi, Alessandro Ianni, Thomas Braun, Yoshihiro Komohara, Masashi Mukoyama, Kazuya Yamagata
• Journal: Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 5927 (04 12 2018) ISSN: 2045-2322 [Electronic] England
• PMID: 29651144 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Sirt7 protein, mouse
• Tumor Necrosis Factor-alpha
• SIRT3 protein, human
• Sirtuin 3
• Sirtuins
• Cisplatin

Topics

• Acute Kidney Injury (chemically induced, genetics, pathology)
• Animals
• Apoptosis (genetics)
• Cisplatin (adverse effects, therapeutic use)
• Humans
• Inflammation (chemically induced, genetics, pathology)
• Kidney (drug effects, injuries, pathology)
• Mice
• Mice, Knockout
• Neoplasms (complications, drug therapy)
• Oxidative Stress (drug effects, genetics)
• Sirtuin 3
• Sirtuins (genetics)
• Tumor Necrosis Factor-alpha (genetics)