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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-07-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231719315502 |
| _version_ | 1818506894071824384 |
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| author | Ruijing Zhang Jason Saredy Ying Shao Tian Yao Lu Liu Fatma Saaoud William Y. Yang Yu Sun Candice Johnson Charles Drummer, IV Hangfei Fu Yifan Lu Keman Xu Ming Liu Jirong Wang Elizabeth Cutler Daohai Yu Xiaohua Jiang Yafeng Li Rongshan Li Lihua Wang Eric T. Choi Hong Wang Xiaofeng Yang |
| author_facet | Ruijing Zhang Jason Saredy Ying Shao Tian Yao Lu Liu Fatma Saaoud William Y. Yang Yu Sun Candice Johnson Charles Drummer, IV Hangfei Fu Yifan Lu Keman Xu Ming Liu Jirong Wang Elizabeth Cutler Daohai Yu Xiaohua Jiang Yafeng Li Rongshan Li Lihua Wang Eric T. Choi Hong Wang Xiaofeng Yang |
| author_sort | Ruijing Zhang |
| collection | DOAJ |
| 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). |
| first_indexed | 2024-12-10T22:10:52Z |
| format | Article |
| id | doaj.art-88f809afc276459f9d4e9c02701e32d1 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-10T22:10:52Z |
| publishDate | 2020-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-88f809afc276459f9d4e9c02701e32d12022-12-22T01:31:36ZengElsevierRedox Biology2213-23172020-07-0134101460End-stage renal disease is different from chronic kidney disease in upregulating ROS-modulated proinflammatory secretome in PBMCs - A novel multiple-hit model for disease progressionRuijing Zhang0Jason Saredy1Ying Shao2Tian Yao3Lu Liu4Fatma Saaoud5William Y. Yang6Yu Sun7Candice Johnson8Charles Drummer, IV9Hangfei Fu10Yifan Lu11Keman Xu12Ming Liu13Jirong Wang14Elizabeth Cutler15Daohai Yu16Xiaohua Jiang17Yafeng Li18Rongshan Li19Lihua Wang20Eric T. Choi21Hong Wang22Xiaofeng Yang23Center for Inflammation, Translational & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA; Department of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030013, China; Department of Nephrology, The Affiliated People's Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030012, ChinaCenters for Metabolic Disease Research, Cardiovascular Research, & Thrombosis Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USACenter for Inflammation, Translational & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USAShanxi Medical University, Taiyuan, Shanxi Province, 030001, ChinaCenters for Metabolic Disease Research, Cardiovascular Research, & Thrombosis Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USACenter for Inflammation, Translational & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USARutgers University, New Brunswick, NJ, 08901, USACenter for Inflammation, Translational & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USACenter for Inflammation, Translational & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USACenter for Inflammation, Translational & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USACenter for Inflammation, Translational & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USACenter for Inflammation, Translational & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USACenter for Inflammation, Translational & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USACenter for Inflammation, Translational & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA; Shanxi Medical University, Taiyuan, Shanxi Province, 030001, ChinaCenter for Inflammation, Translational & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USACenter for Inflammation, Translational & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA; School of Science and Engineering, Tulane University, New Orleans, LA, 70118, USADepartment of Clinical Sciences, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USACenter for Inflammation, Translational & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USADepartment of Nephrology, The Affiliated People's Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030012, ChinaDepartment of Nephrology, The Affiliated People's Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030012, ChinaDepartment of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030013, ChinaDivision of Vascular and Endovascular Surgery, Department of Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA; Centers for Metabolic Disease Research, Cardiovascular Research, & Thrombosis Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA; Departments of Pharmacology, Microbiology and Immunology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USACenters for Metabolic Disease Research, Cardiovascular Research, & Thrombosis Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA; Departments of Pharmacology, Microbiology and Immunology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USACenter for Inflammation, Translational & Clinical Lung Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA; Centers for Metabolic Disease Research, Cardiovascular Research, & Thrombosis Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA; Departments of Pharmacology, Microbiology and Immunology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA; Corresponding author. Centers for Inflammation, Translational & Clinical Lung Research, Metabolic Disease Research, Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine at Temple University, 3500 North Broad Street, MERB-1059, Philadelphia, PA, 19140, USA.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).http://www.sciencedirect.com/science/article/pii/S2213231719315502Chronic kidney disease(CKD)End-stage renal disease(ESRD)PBMC secretomeReactive oxygen species |
| spellingShingle | Ruijing Zhang Jason Saredy Ying Shao Tian Yao Lu Liu Fatma Saaoud William Y. Yang Yu Sun Candice Johnson Charles Drummer, IV Hangfei Fu Yifan Lu Keman Xu Ming Liu Jirong Wang Elizabeth Cutler Daohai Yu Xiaohua Jiang Yafeng Li Rongshan Li Lihua Wang Eric T. Choi Hong Wang Xiaofeng Yang 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 Redox Biology Chronic kidney disease (CKD) End-stage renal disease (ESRD) PBMC secretome Reactive oxygen species |
| 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 | Chronic kidney disease (CKD) End-stage renal disease (ESRD) PBMC secretome Reactive oxygen species |
| url | http://www.sciencedirect.com/science/article/pii/S2213231719315502 |
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