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Hokkaido University Collection of Scholarly and Academic Papers >
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Orosomucoid 1 is involved in the development of chronic allograft rejection after kidney transplantation
| Title: | Orosomucoid 1 is involved in the development of chronic allograft rejection after kidney transplantation |
| Authors: | Higuchi, Haruka Browse this author | | Kamimura, Daisuke Browse this author →KAKEN DB | | Jiang, Jing-Jing Browse this author | | Atsumi, Toru Browse this author →KAKEN DB | | Iwami, Daiki Browse this author →KAKEN DB | | Hotta, Kiyohiko Browse this author →KAKEN DB | | Harada, Hiroshi Browse this author | | Takada, Yusuke Browse this author | | Kanno-Okada, Hiromi Browse this author | | Hatanaka, Kanako C. Browse this author | | Tanaka, Yuki Browse this author →KAKEN DB | | Shinohara, Nobuo Browse this author →KAKEN DB | | Murakami, Masaaki Browse this author →KAKEN DB |
| Keywords: | biomarker | | chronic active antibody-mediated rejection | | chronic kidney allograft rejection | | inflammation amplifier |
| Issue Date: | May-2020 |
| Publisher: | Oxford University Press |
| Journal Title: | International immunology |
| Volume: | 32 |
| Issue: | 5 |
| Start Page: | 335 |
| End Page: | 346 |
| Publisher DOI: | 10.1093/intimm/dxaa003 |
| Abstract: | Chronic allograft rejection is the most common cause of long-term allograft failure. One reason is that current diagnostics and therapeutics for chronic allograft rejection are very limited. We here show that enhanced NF kappa B signaling in kidney grafts contributes to chronic active antibody-mediated rejection (CAAMR), which is a major pathology of chronic kidney allograft rejections. Moreover, we found that urinary orosomucoid 1 (ORM1) is a candidate marker molecule and therapeutic target for CAAMR. Indeed, urinary ORM1 concentration was significantly higher in kidney transplant recipients pathologically diagnosed with CAAMR than in kidney transplant recipients with normal histology, calcineurin inhibitor toxicity, or interstitial fibrosis and tubular atrophy. Additionally, we found that kidney biopsy samples with CAAMR expressed more ORM1 and had higher NF kappa B and STAT3 activation in tubular cells than samples from non-CAAMR samples. Consistently, ORM1 production was induced after cytokine-mediated NF kappa B and STAT3 activation in primary kidney tubular cells. The loss- and gain-of-function of ORM1 suppressed and promoted NF kappa B activation, respectively. Finally, ORM1-enhanced NF kappa B-mediated inflammation development in vivo. These results suggest that an enhanced NF kappa B-dependent pathway following NF kappa B and STAT3 activation in the grafts is involved in the development of chronic allograft rejection after kidney transplantation and that ORM1 is a non-invasive candidate biomarker and possible therapeutic target for chronic kidney allograft rejection. |
| Rights: | This is a pre-copyedited, author-produced version of an article accepted for publication in International Immunology following peer review. The version of record Haruka Higuchi, Daisuke Kamimura, Jing-Jing Jiang, Toru Atsumi, Daiki Iwami, Kiyohiko Hotta, Hiroshi Harada, Yusuke Takada, Hiromi Kanno-Okada, Kanako C Hatanaka, Yuki Tanaka, Nobuo Shinohara, Masaaki Murakami, Orosomucoid 1 is involved in the development of chronic allograft rejection after kidney transplantation, International Immunology, Volume 32, Issue 5, May 2020, Pages 335-346, is available online at: https://doi.org/10.1093/intimm/dxaa003. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/81115 |
| Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 村上 正晃
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