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Kidney Week

Abstract: FR-PO350

12/15-Lipoxygenase Knockout Mice Exhibit a Resistance to Kidney Damage in CKD

Session Information

  • CKD: Mechanisms - II
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Takahashi, Naohiro, Tokyo Medical and Dental University, Tokyo, Japan
  • Kikuchi, Hiroaki, Tokyo Medical and Dental University, Tokyo, Japan
  • Arita, Makoto, RIKEN-IMS, Yokohama, Japan
  • Ando, Fumiaki, Tokyo Medical and Dental University, Tokyo, Japan
  • Mandai, Shintaro, Tokyo Medical and Dental University, Tokyo, Japan
  • Isobe, Kiyoshi, Tokyo Medical and Dental University, Tokyo, Japan
  • Susa, Koichiro, Tokyo Medical and Dental University, Tokyo, Japan
  • Mori, Takayasu, Tokyo Medical and Dental University, Tokyo, Japan
  • Nomura, Naohiro, Tokyo Medical and Dental University, Tokyo, Japan
  • Rai, Tatemitsu, Tokyo Medical and Dental University, Tokyo, Japan
  • Uchida, Shinichi, Tokyo Medical and Dental University, Tokyo, Japan
  • Sohara, Eisei, Tokyo Medical and Dental University, Tokyo, Japan
Background

It has been reported that polyunsaturated fatty acids(PUFA) and their metabolites are related with inflammation and its resolution in several organs. The roles of these metabolites in kidneys, however, have been unclear. In addition, which metabolite is a key player in exacerbation and remission of chronic kidney disease (CKD) remains unknown. 12/15-Lipoxygenase (ALOX15) is one of the key molecules which has a function to produce bioactive lipid metabolites from PUFA. Although there are some reports to present linkage between ALOX15 and inflammatory diseases, it is still unknown whether and how ALOX15 has effects on the progression of CKD.

Methods

Kidney tissue from subtotal nephrectomy mice was analyzed with lipidomics to reveal lipid profiles of CKD kidneys. To establish CKD models, subtotal nephrectomy or oral administration of adenine was performed to C57BL/6J mice and ALOX15 knockout mice. Histologic examination, western blot and quantitative PCR were performed to investigate the phenotype of ALOX15 knockout mice.

Results

Lipidomics analysis revealed that ALOX15-mediated lipid metabolites were significantly decreased in kidneys of mice with subtotal nephrectomy in comparison with those of control mice. Therefore, we examined two CKD models of ALOX15 knockout mice, subtotal nephrectomy and adenine-induced nephropathy. Renal functions of ALOX15 knockout mice were more preserved than those of wild type mice in the both CKD models. Alfa-SMA and NGAL were also suppressed in ALOX15 knockout mice. Quantitative-PCR revealed that mRNA level of alpha-1 type I collagen in kidneys of ALOX15 knockout mice was reduced comparing with that of wild type mice in the both CKD models. Masson's trichrome staining revealed decreased interstitial fibrosis of ALOX15 knockout CKD mice in comparison with wild type mice. These results suggested that reduction of some ALOX15-mediated lipid metabolites which induce renal damage could have beneficial effects on CKD.

Conclusion

Lipidomics of the kidneys from subtotal nephrectomy mice revealed the significant change in the amount of ALOX15-mediated lipid metabolites. ALOX15 knockout mice exhibited a resistant phenotype to CKD. ALOX15 and some ALOX15-mediated lipid metabolites might be novel therapeutic targets of CKD.