Pyruvate Kinase M2: A Novel Biomarker for the Early Detection of Acute Kidney Injury

Cheon, Ji Hyun; Kim, Sun Young; Son, Ji Yeon; Kang, Yun Ju; An, Ji Hye; Kwon, Ji Hoon; Song, Hosub; Moon, Aree; Lee, Byung Mu; Kim, Hyung Sik

doi:10.5487/tr.2016.32.1.047

Cited by 33 publications

(25 citation statements)

References 78 publications

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“…Because of its increased expression and significant changes in cellular metabolism, PKM2 has been identified as a biomarker for tissue damage such as acute kidney injury [18]. PKM2 can regulate gene transcription MEK5 by phosphorylating STAT3, which in turn activates numerous transcriptional factors to regulate cell proliferation, differentiation, migration, and survival [11,12,19].…”

Section: Introductionmentioning

confidence: 99%

Pyruvate Kinase M2 Increases Angiogenesis, Neurogenesis, and Functional Recovery Mediated by Upregulation of STAT3 and Focal Adhesion Kinase Activities After Ischemic Stroke in Adult Mice

et al. 2018

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Ischemic stroke remains a serious threat to human life. Generation of neuronal and vascular cells is an endogenous regenerative mechanism in the adult brain, which may contribute to tissue repair after stroke. However, the regenerative activity is typically insufficient for significant therapeutic effects after brain injuries. Pyruvate kinase isoform M2 (PKM2) is a key regulator for energy metabolism. PKM2 also has nonmetabolic roles involving regulations of gene expression, cell proliferation, and migration in cancer cells as well as noncancerous cells. In a focal ischemic stroke mouse model, recombinant PKM2 (rPKM2) administration (160 ng/kg, intranasal delivery) at 1 h after stroke showed the significant effect of a reduced infarct volume of more the 60%. Delayed treatment of rPKM2, however, lost the acute neuroprotective effect. We then tested a novel hypothesis that delayed treatment of PKM2 might show proregenerative effects for long-term functional recovery and this chronic action could be mediated by its downstream STAT3 signaling. rPKM2 (160 ng/kg) was delivered to the brain using noninvasive intranasal administration 24 h after the stroke and repeated every other day. Western blot analysis revealed that, 7 days after the stroke, the levels of PKM2 and phosphorylated STAT3 and the expression of angiogenic factors VEGF, Ang-1, and Tie-2 in the peri-infarct region were significantly increased in the rPKM2 treatment group compared with those of the stroke vehicle group. To label proliferating cells, 5-bromo-2'-deoxyuridine (BrdU, 50 mg/kg, i.p.) was injected every day starting 3 days after stroke. At 14 days after stroke, immunohistochemistry showed that rPKM2 increased cell homing of doublecortin (DCX)-positive neuroblasts to the ischemic cortex. In neural progenitor cell (NPC) cultures, rPKM2 (0.4-4 nM) increased the expression of integrin β1 and the activation/phosphorylation of focal adhesion kinase (FAK). A mediator role of FAK in PKM2-promoted cell migration was verified in FAK-knockout fibroblast cultures. In the peri-infarct region of the brain, increased numbers of Glut-1/BrdU and NeuN/BrdU double-positive cells indicated enhanced angiogenesis and neurogenesis, respectively, compared to stroke vehicle mice. Using Laser Doppler imaging, we observed better recovery of the local blood flow in the peri-infarct region of rPKM2-treated mice 14 days after stroke. Meanwhile, rPKM2 improved the sensorimotor functional recovery measured by the adhesive removal test. Inhibiting the STAT3 phosphorylation/activation by the STAT3 inhibitor, BP-1-102 (3 mg/kg/day, o.g.), abolished all beneficial effects of rPKM2 in the stroke mice. Taken together, this investigation provides the first evidence demonstrating that early treatment of rPKM2 shows an acute neuroprotective effect against ischemic brain damage, whereas delayed rPKM2 treatment promotes regenerative activities in the poststroke brain leading to better functional recovery. The underlying mechanism involves activation of the STAT3 and FAK signals in the pos...

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Section: Introductionmentioning

confidence: 99%

Pyruvate Kinase M2 Increases Angiogenesis, Neurogenesis, and Functional Recovery Mediated by Upregulation of STAT3 and Focal Adhesion Kinase Activities After Ischemic Stroke in Adult Mice

et al. 2018

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“…Recently, some new potential biomarkers have been proposed for early determination of AKI in specific conditions. Clusterin, osteopontin, glutathione-S-transferase (GST) and pyruvate kinase M2 [52][53][54][55]. All were associated with the development of druginduced nephrotoxicity [55].…”

Section: Other New Potential Biomarkersmentioning

confidence: 99%

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2019

AJUN

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New Biomarkers of AKI Novel AKI biomarkers have made significant contributions to our understanding of the molecular underpinnings of AKI, they could also have use as molecular phenotyping tools that facilitate the identification of patients who could benefit from a specific intervention, even a biomarker-targeted intervention [8]. They were proved to be useful in facilitating early diagnosis, guiding targeted interventions and monitoring the disease progression and resolution [9].

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“…The clinical diagnosis of IRI is routinely based on biochemical and haematological tests (Cheon et al . ; Fuhrman & Kellum, ; Yang et al . ).…”

Section: Introductionmentioning

confidence: 99%

“…However, biochemical markers, such as serum creatinine and urinary microprotein, cannot evaluate the function of a single kidney (Cheon et al . ; Fuhrman & Kellum, ; Yang et al . ).…”

Section: Introductionmentioning

confidence: 99%

Magnetic resonance imaging evaluation of renal ischaemia–reperfusion injury in a rabbit model

Pan¹,

Chen

Xing³

et al. 2017

Experimental Physiology

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What is the central question of this study? Renal ischaemia-reperfusion injury occurs in various clinical settings. The clinical diagnosis of ischaemia-reperfusion injury is routinely based on biochemical and haematological tests, which cannot evaluate the function of a single kidney. New magnetic resonance imaging techniques to identify the pathophysiological changes in the renal outer medulla were evaluated. What is the main finding and its importance? This study demonstrated that susceptibility-weighted imaging is a feasible non-invasive tool for imaging and evaluating physipathological changes in the renal outer medulla after ischaemia-reperfusion injury. The aim was to evaluate the feasibility of susceptibility-weighted imaging (SWI) as a tool to identify the changes in the renal outer medulla (OM) in a rabbit model of renal ischaemia-reperfusion injury (IRI). New Zealand rabbits were used (control group n = 10; IRI group n = 40). The rabbits in the IRI group were subjected to left renal artery clamping for 60 min. T2-weighted (T2WI) and SWI examinations were performed at 1, 12, 24 or 48 h after reperfusion (each n = 10). After the examinations, the kidneys were submitted to histological evaluation. The contrast-to-noise ratio (CNR) for the left renal OM was measured using T2WI and SWI. The T2WI and SWI scores of the integrity of the renal OM were evaluated. There were significant differences between T2WI CNRs and SWI CNRs in the control group and the IRI 1, 12 and 48 h time points (all P < 0.05). No significant difference was found between T2WI and SWI CNRs at IRI 24 h (P > 0.05). The mean SWI scores of renal OM in the IRI 1 and 12 h subgroups were both significantly lower than that in the control group (all P < 0.05). The only significant difference in the mean T2WI scores of renal OM was observed between the control and IRI 1 h groups (P < 0.05). Susceptibility-weighted imaging has a significant advantage in evaluation of healthy renal OM over conventional magnetic resonance imaging, and it is a feasible non-invasive tool for imaging and evaluating changes in the renal OM after IRI.

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Pyruvate Kinase M2: A Novel Biomarker for the Early Detection of Acute Kidney Injury

Cited by 33 publications

References 78 publications

Pyruvate Kinase M2 Increases Angiogenesis, Neurogenesis, and Functional Recovery Mediated by Upregulation of STAT3 and Focal Adhesion Kinase Activities After Ischemic Stroke in Adult Mice

Pyruvate Kinase M2 Increases Angiogenesis, Neurogenesis, and Functional Recovery Mediated by Upregulation of STAT3 and Focal Adhesion Kinase Activities After Ischemic Stroke in Adult Mice

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Magnetic resonance imaging evaluation of renal ischaemia–reperfusion injury in a rabbit model

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