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Midkine promotes kidney injury in diabetic kidney disease by increasing neutrophil extracellular traps formation

BACKGROUND: We sought to investigate the role of midkine (MK) on neutrophil extracellular trap formation (NETosis) and diabetic kidney disease (DKD) progression. METHODS: The expression of MK and NETosis in the renal tissue of DKD patients was examined by immunohistochemistry and immunofluorescence,...

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Autores principales: Liu, Gaohong, Ren, Xiaojun, Li, Yousong, Li, Han
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279803/
https://www.ncbi.nlm.nih.gov/pubmed/35845498
http://dx.doi.org/10.21037/atm-22-2382
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author Liu, Gaohong
Ren, Xiaojun
Li, Yousong
Li, Han
author_facet Liu, Gaohong
Ren, Xiaojun
Li, Yousong
Li, Han
author_sort Liu, Gaohong
collection PubMed
description BACKGROUND: We sought to investigate the role of midkine (MK) on neutrophil extracellular trap formation (NETosis) and diabetic kidney disease (DKD) progression. METHODS: The expression of MK and NETosis in the renal tissue of DKD patients was examined by immunohistochemistry and immunofluorescence, respectively. Neutrophils extracted from mouse bone marrow by gradient centrifugation were treated with MK for this in-vitro study. A mouse diabetes model was induced by a high-fat diet combined with an intraperitoneal injection of streptozocin (STZ). Antisense oligodeoxynucleotide (ODN) for MK inhibition was administered via tail vein injection. RESULTS: We found that the expression of MK was increased in the kidney tissue of DKD patients. Additionally, a greater number of neutrophils were primed toward NETosis in the kidney tissue of DKD patients, which was manifested by the increased expression of NETosis biomarkers citrullinated histone H3 (H3Cit) and myeloperoxidase (MPO). In vitro, MK treatment concentration-dependently increased neutrophil proliferation (cell counting kit-8). Further, western blot and enzyme-linked immunosorbent assays showed that MK (100 ng/mL) significantly promoted NETosis and the expression of inflammatory factors interleukin (IL)-1 and IL-6 secretion in high-glucose treated neutrophils. In the mouse diabetes model, MK promoted the pathological damage and fibrosis of kidney tissue, as demonstrated by the reversion of the pathological damage and fibrosis by the MK antisense ODN [diabetes mellitus (DM) + MK – ODN] treatment. Additionally, the inhibition of MK reduced the formation of NETs. CONCLUSIONS: MK promotes DKD progression by increasing NETosis.
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spelling pubmed-92798032022-07-15 Midkine promotes kidney injury in diabetic kidney disease by increasing neutrophil extracellular traps formation Liu, Gaohong Ren, Xiaojun Li, Yousong Li, Han Ann Transl Med Original Article BACKGROUND: We sought to investigate the role of midkine (MK) on neutrophil extracellular trap formation (NETosis) and diabetic kidney disease (DKD) progression. METHODS: The expression of MK and NETosis in the renal tissue of DKD patients was examined by immunohistochemistry and immunofluorescence, respectively. Neutrophils extracted from mouse bone marrow by gradient centrifugation were treated with MK for this in-vitro study. A mouse diabetes model was induced by a high-fat diet combined with an intraperitoneal injection of streptozocin (STZ). Antisense oligodeoxynucleotide (ODN) for MK inhibition was administered via tail vein injection. RESULTS: We found that the expression of MK was increased in the kidney tissue of DKD patients. Additionally, a greater number of neutrophils were primed toward NETosis in the kidney tissue of DKD patients, which was manifested by the increased expression of NETosis biomarkers citrullinated histone H3 (H3Cit) and myeloperoxidase (MPO). In vitro, MK treatment concentration-dependently increased neutrophil proliferation (cell counting kit-8). Further, western blot and enzyme-linked immunosorbent assays showed that MK (100 ng/mL) significantly promoted NETosis and the expression of inflammatory factors interleukin (IL)-1 and IL-6 secretion in high-glucose treated neutrophils. In the mouse diabetes model, MK promoted the pathological damage and fibrosis of kidney tissue, as demonstrated by the reversion of the pathological damage and fibrosis by the MK antisense ODN [diabetes mellitus (DM) + MK – ODN] treatment. Additionally, the inhibition of MK reduced the formation of NETs. CONCLUSIONS: MK promotes DKD progression by increasing NETosis. AME Publishing Company 2022-06 /pmc/articles/PMC9279803/ /pubmed/35845498 http://dx.doi.org/10.21037/atm-22-2382 Text en 2022 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Liu, Gaohong
Ren, Xiaojun
Li, Yousong
Li, Han
Midkine promotes kidney injury in diabetic kidney disease by increasing neutrophil extracellular traps formation
title Midkine promotes kidney injury in diabetic kidney disease by increasing neutrophil extracellular traps formation
title_full Midkine promotes kidney injury in diabetic kidney disease by increasing neutrophil extracellular traps formation
title_fullStr Midkine promotes kidney injury in diabetic kidney disease by increasing neutrophil extracellular traps formation
title_full_unstemmed Midkine promotes kidney injury in diabetic kidney disease by increasing neutrophil extracellular traps formation
title_short Midkine promotes kidney injury in diabetic kidney disease by increasing neutrophil extracellular traps formation
title_sort midkine promotes kidney injury in diabetic kidney disease by increasing neutrophil extracellular traps formation
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279803/
https://www.ncbi.nlm.nih.gov/pubmed/35845498
http://dx.doi.org/10.21037/atm-22-2382
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