The role of senescence of bone marrow cells in acute kidney injury

Liu, Junyong; Ko, Yoon Sook; Lee, Hee Young; Yang, Jihyun; Oh, Se Won; Jo, Sang Kyung; Cho, Won-Yong; Kim, Myung Gyu

doi:10.23876/j.krcp.18.0114

Cited by 7 publications

(5 citation statements)

References 22 publications

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“…In contrast to current data showing persistent inflammation, our group previously demonstrated that young mice who were transplanted with senescent bone marrow (BM) from aged mice demonstrated significantly attenuated kidney inflammation and injury, as compared to aged mice transplanted with BM from young mice 26 . This clear discrepancy in the phenotype of post-ischemic senescent immune cells led us to hypothesize that the intrarenal microenvironment surrounding immune cells might be more important in driving macrophage polarization.…”

Section: Discussioncontrasting

confidence: 72%

Impact of aging on transition of acute kidney injury to chronic kidney disease

Kim

Yang

et al. 2019

Sci Rep

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Acute kidney injury (AKI) increases the risk of end stage renal disease among the elderly, but the precise underlying mechanism is unknown. We investigated the effects of aging on AKI-to-chronic kidney disease (CKD) transition, focusing on renal inflammation. Aged and young C57BL/6 mice were subjected to bilateral ischemia-reperfusion injury (IRI). Baseline proinflammatory cytokine levels of kidneys were elevated in aged mice. After IRI, aged mice also showed persistent M1 dominant inflammation, with increased proinflammatory cytokines during the recovery phase. Persistent M1 inflammation was associated with blunted activation of CSF-1/IRF4 signal for M1/M2 polarization, but in vitro macrophage polarization with cytokine stimulation was not different between young and aged mononuclear cells. The tubular expressions of cell cycle arrest markers increased in aged mice during recovery phase, and in vitro transwell experiments showed that mononuclear cells or M1 macrophages co-cultured with arrested proximal tubular cells at G1 phase significantly impaired M2 polarization, suggesting that prolonged G1 arrest might be involved in persistent M1 inflammation in aged mice. Finally, M1 dominant inflammation in aged mice resulted in fibrosis progression. Our data show that impaired M2 polarization partially driven by senescent tubule cells with cell-cycle arrest may lead to an accelerated progression to CKD in the elderly.

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Section: Discussioncontrasting

confidence: 72%

Impact of aging on transition of acute kidney injury to chronic kidney disease

Kim

Yang

et al. 2019

Sci Rep

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“…Our study showed an increase in blood cytokine consistent with previous reports [5]. These cytokines might be involved with lung injury.…”

Section: Discussionsupporting

confidence: 93%

Change of surfactant protein D and A after renal ischemia reperfusion injury

et al. 2019

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Acute kidney injury (AKI) is associated with widespread effects on distant organs, including the lungs. Surfactant protein (SP)-A and SP-D are members of the C-type lectin family, which plays a critical role in host defense and regulation of inflammation in a variety of infections. Serum levels of SP-A and SP-D are markers to reflect lung injury in acute respiratory distress syndrome, idiopathic pulmonary fibrosis, and sarcoidosis. We investigated the change of lung-specific markers, including SP-A and SP-D in an AKI mice model. We studied C57BL/6J mice 4 and 24 hours after an episode of ischemic AKI (23 min of renal pedicle clamping and then reperfusion); numerous derangements were present, including SP-A, SP-D, and lung tight-junction protein. Neutrophil infiltration and apoptosis in the lungs increased in ischemic AKI. Receptor for advanced glycation end products (RAGE) in the lungs, a marker of pneumocyte I, was not changed. Lung tight-junction proteins, particularly claudin-4, claudin-18, and anti-junctional adhesion molecule 1 (JAMA-1), were reduced in 24 hours after AKI. Serum SP-A and SP-D significantly increased in ischemic AKI. SP-A and SP-D in the lungs did not increase in ischemic AKI. The immunohistochemistry showed that the expression of SP-A and SP-D was intact in ischemic AKI. SP-A and SP-D in the kidneys were significantly higher in AKI than in the sham. These patterns of SP-A and SP-D in the kidneys were similar to those of serum. AKI induces apoptosis and inflammation in the lungs. Serum SP-A and SP-D increased in ischemic AKI, but these could have originated from the kidneys. So serum SP-A and SP-D could not reflect lung injury in AKI. Further study is needed to reveal how a change in lung tight-junction protein could influence the prognosis in patients with AKI.

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“…Moreover, the incidence and severity of AKI increase with age [21]. AKI is associated with an increased risk of mortality, hospitalization, and other comorbidities, such as cardiovascular events [22]. In addition to acute-phase problems associated with AKI, insufficient recovery from AKI, which results in a prolonged decrease in renal function and progression to CKD, is a contributing factor to the increase in the prevalence of reduced kidney function in the elderly [23].…”

Section: Discussionmentioning

confidence: 99%

Impaired NRF2 Inhibits Recovery from Ischemic Reperfusion Injury in the Aging Kidney

Kim

Bae

et al. 2023

Antioxidants

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Deteriorating kidney function is frequently observed in the elderly population, as well as vulnerability to acute kidney failure, such as ischemic/reperfusion injury (IRI), and inadequate recovery from IRI is one of the mechanisms of kidney dysfunction in the elderly. The potential mediators in the progression of kidney dysfunction in the aging kidney have not yet been clearly revealed. In this study, we investigated the role of nuclear factor erythroid 2-related factor 2 (NRF2), which is an essential regulator of cellular redox homeostasis, in restoring kidney function after IRI in the aging kidney. NRF2 expression decreased significantly in the kidneys of old mice, as well as histologic and functional renal recovery after IRI; 45-min renal pedicle clamping was retarded in old compared with young mice. Persistent renal injury during the recovery phase after IRI was aggravated in NRF2 knockout (KO) mice compared to wild-type mice. Oxidative stress occurred in NRF2 KO old mice during the IRI recovery phase along with decreased expression of mitochondrial OXPHOS-related proteins and a reduction in mitochondrial ATP content. In vitro, hypoxia/reoxygenation (H/R) injury was aggravated in senescent human proximal tubuloepithelial cells after NRF2 restriction using NRF2 siRNA, which also increased the level of oxidative stress and deteriorated mitochondrial dysfunction. Treating the mice with an NRF2 activator, CDDO-Me, alleviated the injury. These results suggest that NRF2 may be a therapeutic target for the aging kidney.

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The role of senescence of bone marrow cells in acute kidney injury

Cited by 7 publications

References 22 publications

Impact of aging on transition of acute kidney injury to chronic kidney disease

Impact of aging on transition of acute kidney injury to chronic kidney disease

Change of surfactant protein D and A after renal ischemia reperfusion injury

Impaired NRF2 Inhibits Recovery from Ischemic Reperfusion Injury in the Aging Kidney

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