TY - JOUR
T1 - Dialysis-related transcriptomic profiling: The pivotal role of heparanase
AU - Zaza, Gianluigi
AU - Masola, Valentina
AU - Granata, Simona
AU - Pontrelli, Paola
AU - Sallustio, Fabio
AU - Gesualdo, Loreto
AU - Gambaro, Giovanni
AU - Grandaliano, Giuseppe
AU - Lupo, Antonio
PY - 2014
Y1 - 2014
N2 - Peritoneal (PD) and hemodialysis (HD) represent the leading renal replacement therapies in advanced chronic kidney disease (CKD). Although absolutely necessary to ensure patient survival, these treatments are responsible for considerable biological alterations primarily due to the un-physiological contact of blood and tissues with bioincompatible devices or plastificants. Although extensively described, this complex dialysis-related deregulated bio-molecular machinery is still not completely known. Therefore, to select a set of genes deregulated in patients on dialysis treatment and to assess the possible differences between dialysis modalities, we measured the expression level of 132 genes involved in proteoglycans (PGs) biosynthesis/metabolism by microarray in peripheral blood mononuclear cells (PBMCs), biological elements involved in the inflammatory/immune response, from 5 healthy subjects (HS), 9 CKD, 10 PD, and 17 HD patients. We focused on PGs biosynthesis/metabolism pathways because of their involvement in the onset and development of several CKD-related clinical complications. Statistical analysis/bioinformatics identified 70 genes discriminating HD/PD patients from HS/CKD subjects (P < 0.009, FDR < 5%). Twenty-five genes were up-regulated (e.g. HPSE, VCAN, and VEGFA) and 45 down-regulated (e.g. IDS and HEXA) in PD/HD compared to HS/CKD. Gene expression and plasma activity of Heparanase (HPSE), one of the top selected up-regulated genes in PD/HD, validated microarray results. In addition, for the second part of the study, HPSE plasmatic activities were first assessed in an independent testing-group (7 HS, 10 CKD, 17 PD, and 11 HD), and then correlated with high-sensitive C reactive protein (HS-CRP) measurements. HPSE activity was higher in PD and HD versus CKD/HS and it correlated with HS-CRP levels (R (2 )= 0.37, P = 0.007). Lipopolysaccharide (LPS)-stimulated PBMCs showed a significant up-regulation of HPSE mRNA level (P = 0.04). Our results revealed that dialysis treatments induce change in the transcriptomic pattern of biosynthetic proteoglycans in PBMCs with an up-regulation of HPSE. Our selected genes could be useful in the future as potential biomarkers and new therapeutic targets.
AB - Peritoneal (PD) and hemodialysis (HD) represent the leading renal replacement therapies in advanced chronic kidney disease (CKD). Although absolutely necessary to ensure patient survival, these treatments are responsible for considerable biological alterations primarily due to the un-physiological contact of blood and tissues with bioincompatible devices or plastificants. Although extensively described, this complex dialysis-related deregulated bio-molecular machinery is still not completely known. Therefore, to select a set of genes deregulated in patients on dialysis treatment and to assess the possible differences between dialysis modalities, we measured the expression level of 132 genes involved in proteoglycans (PGs) biosynthesis/metabolism by microarray in peripheral blood mononuclear cells (PBMCs), biological elements involved in the inflammatory/immune response, from 5 healthy subjects (HS), 9 CKD, 10 PD, and 17 HD patients. We focused on PGs biosynthesis/metabolism pathways because of their involvement in the onset and development of several CKD-related clinical complications. Statistical analysis/bioinformatics identified 70 genes discriminating HD/PD patients from HS/CKD subjects (P < 0.009, FDR < 5%). Twenty-five genes were up-regulated (e.g. HPSE, VCAN, and VEGFA) and 45 down-regulated (e.g. IDS and HEXA) in PD/HD compared to HS/CKD. Gene expression and plasma activity of Heparanase (HPSE), one of the top selected up-regulated genes in PD/HD, validated microarray results. In addition, for the second part of the study, HPSE plasmatic activities were first assessed in an independent testing-group (7 HS, 10 CKD, 17 PD, and 11 HD), and then correlated with high-sensitive C reactive protein (HS-CRP) measurements. HPSE activity was higher in PD and HD versus CKD/HS and it correlated with HS-CRP levels (R (2 )= 0.37, P = 0.007). Lipopolysaccharide (LPS)-stimulated PBMCs showed a significant up-regulation of HPSE mRNA level (P = 0.04). Our results revealed that dialysis treatments induce change in the transcriptomic pattern of biosynthetic proteoglycans in PBMCs with an up-regulation of HPSE. Our selected genes could be useful in the future as potential biomarkers and new therapeutic targets.
KW - Peritoneal dialysis
KW - hemodialysis
KW - heparanase
KW - microarray
KW - microinflammation
KW - proteoglycans
KW - Peritoneal dialysis
KW - hemodialysis
KW - heparanase
KW - microarray
KW - microinflammation
KW - proteoglycans
UR - http://hdl.handle.net/10807/51181
U2 - 10.1177/1535370213506678
DO - 10.1177/1535370213506678
M3 - Article
SN - 1535-3699
VL - 239
SP - 52
EP - 64
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
ER -