Kidney Research and Clinical Practice 2019 Mar; 38(1): 25-32  https://doi.org/10.23876/j.krcp.18.0114
The role of senescence of bone marrow cells in acute kidney injury
Junyong Lee, Yoon Sook Ko, Hee Young Lee, Jihyun Yang, Sewon Oh, Sang-Kyung Jo, Wonyong Cho, Myung-Gyu Kim
Department of Internal Medicine, Korea University Medical College, Seoul, Korea
Correspondence to: Myung-Gyu Kim, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 73 Inchon-ro, Seongbuk-gu, Seoul 02841, Korea. E-mail: myung-gyu@korea.ac.kr
ORCID: https://orcid.org/0000-0001-8807-2452
Received: September 18, 2018; Revised: November 15, 2018; Accepted: December 1, 2018; Published online: March 31, 2019.
© The Korean Society of Nephrology. All rights reserved.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background: The prevalence of acute kidney injury (AKI) in elderly patients has grown considerably. Age-associated changes in the immune system can be one of the critical factors determining AKI outcomes. This study aimed to investigate the role of senescence of bone marrow (BM)-derived cells in the development of AKI, focusing on the immune response.
Methods: Female 7-week-old C57BL/6 mice were irradiated and treated with BM cells from either 48-week-old or 8-week-old male mice. Ischemia-reperfusion injury (IRI) was induced, and their functional deterioration, histological tubular damage, and inflammatory responses were compared. For the in vitro study, lipopolysaccharide (LPS)-stimulated cytokine production by BM cells from old and young mice were examined.
Results: At 24 hours after IRI, there was no significant difference in the number of circulating immune cells between the mice transplanted with old or young BM cells. However, the mice with old BM cells showed less functional deterioration and histological tubular injury than those with young BM cells. Moreover, macrophage infiltration and renal cytokine interleukin (IL)-12 levels were lower in the mice with old BM cells at 24 hours post-IRI. Consistently, the in vitro study showed that LPS-induced production of cytokines interferon-γ, monocyte chemoattractant protein-1, and IL-10 was attenuated in cultured old BM cells, suggesting that age-related functional changes in these cells may lead to reduced inflammation in IRI.
Conclusion: Immunosenescence could affect the susceptibility and response to renal IRI. Further studies specifically addressing age-related alterations can help in the development of treatment strategies for elderly patients with AKI.
Keywords: Acute kidney injury, Aging, Immunosenescence, Ischemia reperfusion injury


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