A bioinspired carbon monoxide delivery system prevents acute kidney injury and the progression to chronic kidney disease

Taisei Nagasaki, Hitoshi Maeda, Kazuaki Taguchi, Hiroki Yanagisawa, Kento Nishida, Kazuki Kobayashi, Naoki Wada, Isamu Noguchi, Ryota Murata, Hiromi Sakai, Hiroaki Kitagishi, Junji Saruwatari, Hiroshi Watanabe, Masaki Otagiri, Toru Maruyama

研究成果: Article査読

抄録

Renal ischemia-reperfusion (IR)-induced tissue hypoxia causes impaired energy metabolism and oxidative stress. These conditions lead to tubular cell damage, which is a cause of acute kidney injury (AKI) and AKI to chronic kidney disease (CKD). Three key molecules, i.e., hypoxia-inducible factor-1α (HIF-1α), AMP-activated protein kinase (AMPK), and nuclear factor E2-related factor 2 (Nrf2), have the potential to protect tubular cells from these disorders. Although carbon monoxide (CO) can comprehensively induce these three molecules via the action of mitochondrial reactive oxygen species (mtROS), the issue of whether CO induces these molecules in tubular cells remains unclear. Herein, we report that CO-enriched red blood cells (CO-RBC) cell therapy, the inspiration for which is the in vivo CO delivery system, exerts a renoprotective effect on hypoxia-induced tubular cell damage via the upregulation of the above molecules. Experiments using a mitochondria-specific antioxidant provide evidence to show that CO-driven mtROS partially contributes to the upregulation of the aforementioned molecules in tubular cells. CO-RBC ameliorates the pathological conditions of IR-induced AKI model mice via activation of these molecules. CO-RBC also prevents renal fibrosis via the suppression of epithelial mesenchymal transition and transforming growth factor-β1 secretion in an IR-induced AKI to CKD model mice. In conclusion, our results confirm that the bioinspired CO delivery system prevents the pathological conditions of both AKI and AKI to CKD via the amelioration of hypoxia inducible tubular cell damage, thereby making it an effective cell therapy for treating the progression to CKD.

本文言語English
論文番号102371
ジャーナルRedox Biology
54
DOI
出版ステータスPublished - 2022 8月

ASJC Scopus subject areas

  • 有機化学
  • 臨床生化学

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