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End-stage renal disease is different from chronic kidney disease in upregulating ROS-modulated proinflammatory secretome in PBMCs - A novel multiple-hit model for disease progression

BACKGROUND: The molecular mechanisms underlying chronic kidney disease (CKD) transition to end-stage renal disease (ESRD) and CKD acceleration of cardiovascular and other tissue inflammations remain poorly determined. METHODS: We conducted a comprehensive data analyses on 7 microarray datasets in pe...

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Autores principales: Zhang, Ruijing, Saredy, Jason, Shao, Ying, Yao, Tian, Liu, Lu, Saaoud, Fatma, Yang, William Y., Sun, Yu, Johnson, Candice, Drummer, Charles, Fu, Hangfei, Lu, Yifan, Xu, Keman, Liu, Ming, Wang, Jirong, Cutler, Elizabeth, Yu, Daohai, Jiang, Xiaohua, Li, Yafeng, Li, Rongshan, Wang, Lihua, Choi, Eric T., Wang, Hong, Yang, Xiaofeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327976/
https://www.ncbi.nlm.nih.gov/pubmed/32179051
http://dx.doi.org/10.1016/j.redox.2020.101460
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author Zhang, Ruijing
Saredy, Jason
Shao, Ying
Yao, Tian
Liu, Lu
Saaoud, Fatma
Yang, William Y.
Sun, Yu
Johnson, Candice
Drummer, Charles
Fu, Hangfei
Lu, Yifan
Xu, Keman
Liu, Ming
Wang, Jirong
Cutler, Elizabeth
Yu, Daohai
Jiang, Xiaohua
Li, Yafeng
Li, Rongshan
Wang, Lihua
Choi, Eric T.
Wang, Hong
Yang, Xiaofeng
author_facet Zhang, Ruijing
Saredy, Jason
Shao, Ying
Yao, Tian
Liu, Lu
Saaoud, Fatma
Yang, William Y.
Sun, Yu
Johnson, Candice
Drummer, Charles
Fu, Hangfei
Lu, Yifan
Xu, Keman
Liu, Ming
Wang, Jirong
Cutler, Elizabeth
Yu, Daohai
Jiang, Xiaohua
Li, Yafeng
Li, Rongshan
Wang, Lihua
Choi, Eric T.
Wang, Hong
Yang, Xiaofeng
author_sort Zhang, Ruijing
collection PubMed
description BACKGROUND: The molecular mechanisms underlying chronic kidney disease (CKD) transition to end-stage renal disease (ESRD) and CKD acceleration of cardiovascular and other tissue inflammations remain poorly determined. METHODS: We conducted a comprehensive data analyses on 7 microarray datasets in peripheral blood mononuclear cells (PBMCs) from patients with CKD and ESRD from NCBI-GEO databases, where we examined the expressions of 2641 secretome genes (SG). RESULTS: 1) 86.7% middle class (molecular weight >500 Daltons) uremic toxins (UTs) were encoded by SGs; 2) Upregulation of SGs in PBMCs in patients with ESRD (121 SGs) were significantly higher than that of CKD (44 SGs); 3) Transcriptomic analyses of PBMC secretome had advantages to identify more comprehensive secretome than conventional secretomic analyses; 4) ESRD-induced SGs had strong proinflammatory pathways; 5) Proinflammatory cytokines-based UTs such as IL-1β and IL-18 promoted ESRD modulation of SGs; 6) ESRD-upregulated co-stimulation receptors CD48 and CD58 increased secretomic upregulation in the PBMCs, which were magnified enormously in tissues; 7) M1-, and M2-macrophage polarization signals contributed to ESRD- and CKD-upregulated SGs; 8) ESRD- and CKD-upregulated SGs contained senescence-promoting regulators by upregulating proinflammatory IGFBP7 and downregulating anti-inflammatory TGF-β1 and telomere stabilizer SERPINE1/PAI-1; 9) ROS pathways played bigger roles in mediating ESRD-upregulated SGs (11.6%) than that in CKD-upregulated SGs (6.8%), and half of ESRD-upregulated SGs were ROS-independent. CONCLUSIONS: Our analysis suggests novel secretomic upregulation in PBMCs of patients with CKD and ESRD, act synergistically with uremic toxins, to promote inflammation and potential disease progression. Our findings have provided novel insights on PBMC secretome upregulation to promote disease progression and may lead to the identification of new therapeutic targets for novel regimens for CKD, ESRD and their accelerated cardiovascular disease, other inflammations and cancers. (Total words: 279).
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spelling pubmed-73279762020-07-06 End-stage renal disease is different from chronic kidney disease in upregulating ROS-modulated proinflammatory secretome in PBMCs - A novel multiple-hit model for disease progression Zhang, Ruijing Saredy, Jason Shao, Ying Yao, Tian Liu, Lu Saaoud, Fatma Yang, William Y. Sun, Yu Johnson, Candice Drummer, Charles Fu, Hangfei Lu, Yifan Xu, Keman Liu, Ming Wang, Jirong Cutler, Elizabeth Yu, Daohai Jiang, Xiaohua Li, Yafeng Li, Rongshan Wang, Lihua Choi, Eric T. Wang, Hong Yang, Xiaofeng Redox Biol Articles from the Special Issue on Redox Signalling and Cardiovascular Disease; Edited by Christopher Kevil and Yabing Chen BACKGROUND: The molecular mechanisms underlying chronic kidney disease (CKD) transition to end-stage renal disease (ESRD) and CKD acceleration of cardiovascular and other tissue inflammations remain poorly determined. METHODS: We conducted a comprehensive data analyses on 7 microarray datasets in peripheral blood mononuclear cells (PBMCs) from patients with CKD and ESRD from NCBI-GEO databases, where we examined the expressions of 2641 secretome genes (SG). RESULTS: 1) 86.7% middle class (molecular weight >500 Daltons) uremic toxins (UTs) were encoded by SGs; 2) Upregulation of SGs in PBMCs in patients with ESRD (121 SGs) were significantly higher than that of CKD (44 SGs); 3) Transcriptomic analyses of PBMC secretome had advantages to identify more comprehensive secretome than conventional secretomic analyses; 4) ESRD-induced SGs had strong proinflammatory pathways; 5) Proinflammatory cytokines-based UTs such as IL-1β and IL-18 promoted ESRD modulation of SGs; 6) ESRD-upregulated co-stimulation receptors CD48 and CD58 increased secretomic upregulation in the PBMCs, which were magnified enormously in tissues; 7) M1-, and M2-macrophage polarization signals contributed to ESRD- and CKD-upregulated SGs; 8) ESRD- and CKD-upregulated SGs contained senescence-promoting regulators by upregulating proinflammatory IGFBP7 and downregulating anti-inflammatory TGF-β1 and telomere stabilizer SERPINE1/PAI-1; 9) ROS pathways played bigger roles in mediating ESRD-upregulated SGs (11.6%) than that in CKD-upregulated SGs (6.8%), and half of ESRD-upregulated SGs were ROS-independent. CONCLUSIONS: Our analysis suggests novel secretomic upregulation in PBMCs of patients with CKD and ESRD, act synergistically with uremic toxins, to promote inflammation and potential disease progression. Our findings have provided novel insights on PBMC secretome upregulation to promote disease progression and may lead to the identification of new therapeutic targets for novel regimens for CKD, ESRD and their accelerated cardiovascular disease, other inflammations and cancers. (Total words: 279). Elsevier 2020-02-20 /pmc/articles/PMC7327976/ /pubmed/32179051 http://dx.doi.org/10.1016/j.redox.2020.101460 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Articles from the Special Issue on Redox Signalling and Cardiovascular Disease; Edited by Christopher Kevil and Yabing Chen
Zhang, Ruijing
Saredy, Jason
Shao, Ying
Yao, Tian
Liu, Lu
Saaoud, Fatma
Yang, William Y.
Sun, Yu
Johnson, Candice
Drummer, Charles
Fu, Hangfei
Lu, Yifan
Xu, Keman
Liu, Ming
Wang, Jirong
Cutler, Elizabeth
Yu, Daohai
Jiang, Xiaohua
Li, Yafeng
Li, Rongshan
Wang, Lihua
Choi, Eric T.
Wang, Hong
Yang, Xiaofeng
End-stage renal disease is different from chronic kidney disease in upregulating ROS-modulated proinflammatory secretome in PBMCs - A novel multiple-hit model for disease progression
title End-stage renal disease is different from chronic kidney disease in upregulating ROS-modulated proinflammatory secretome in PBMCs - A novel multiple-hit model for disease progression
title_full End-stage renal disease is different from chronic kidney disease in upregulating ROS-modulated proinflammatory secretome in PBMCs - A novel multiple-hit model for disease progression
title_fullStr End-stage renal disease is different from chronic kidney disease in upregulating ROS-modulated proinflammatory secretome in PBMCs - A novel multiple-hit model for disease progression
title_full_unstemmed End-stage renal disease is different from chronic kidney disease in upregulating ROS-modulated proinflammatory secretome in PBMCs - A novel multiple-hit model for disease progression
title_short End-stage renal disease is different from chronic kidney disease in upregulating ROS-modulated proinflammatory secretome in PBMCs - A novel multiple-hit model for disease progression
title_sort end-stage renal disease is different from chronic kidney disease in upregulating ros-modulated proinflammatory secretome in pbmcs - a novel multiple-hit model for disease progression
topic Articles from the Special Issue on Redox Signalling and Cardiovascular Disease; Edited by Christopher Kevil and Yabing Chen
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327976/
https://www.ncbi.nlm.nih.gov/pubmed/32179051
http://dx.doi.org/10.1016/j.redox.2020.101460
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