Identification of Immune-Related Genes as Biomarkers for Uremia DOI Creative Commons

Dongning Lyu,

Guangyu He,

Kan Zhou

et al.

International Journal of General Medicine, Journal Year: 2023, Volume and Issue: Volume 16, P. 5633 - 5649

Published: Nov. 1, 2023

Uremia, which is characterized by immunodeficiency, associated with the deterioration of kidney function. Immune-related genes (IRGs) are crucial for uremia progression.The co-expression network was constructed to identify key modular uremia. IRGs were intersected differentially expressed (DEGs) between and control groups obtain (DEIRGs). DEIRGs subjected functional enrichment analysis. The protein-protein interaction (PPI) constructed. candidate identified using cytoHubba tool. biomarkers various machine learning algorithms. diagnostic value evaluated receiver operating characteristic (ROC) immune infiltration analysis implemented. biological pathways gene set ingenuity pathway mRNA expression validated blood samples patients healthy subjects quantitative real-time polymerase chain reaction (qRT-PCR).In total, four (PDCD1, NGF, PDGFRB, ZAP70) methods. ROC demonstrated that area under curve values individual > 0.9, indicating good power. nomogram model exhibited predictive proportions six cells significantly varied groups. ZAP70 positively correlated resting natural killer (NK) cells, naïve B regulatory T cells. Functional revealed mainly translational function neuroactive ligand-receptor interaction. regulated NK cell signaling. PDCD1 NGF levels determined qRT-PCR consistent those bioinformatics analysis.PDCD1, as uremia, providing a theoretical foundation diagnosis.

Language: Английский

Platelets, inflammation, and purinergic receptors in chronic kidney disease DOI
Adam Corken,

Vincz Ong,

Rajshekhar A. Kore

et al.

Kidney International, Journal Year: 2024, Volume and Issue: 106(3), P. 392 - 399

Published: May 29, 2024

Language: Английский

Citations

4
Colony stimulating factor-1 receptor drives glomerular parietal epithelial cell activation in focal segmental glomerulosclerosis DOI Creative Commons
Josep M. Cruzado, Anna Manonelles, Sandra Rayego‐Mateos

et al.

Kidney International, Journal Year: 2024, Volume and Issue: 106(1), P. 67 - 84

Published: Feb. 28, 2024

Parietal epithelial cells (PECs) are kidney progenitor with similarities to a bone marrow stem cell niche. In focal segmental glomerulosclerosis (FSGS) PECs become activated and contribute extracellular matrix deposition. Colony stimulating factor-1 (CSF-1), hematopoietic growth factor, acts via its specific receptor, CSF-1R, has been implicated in several glomerular diseases, although role on PEC activation is unknown. Here, we found that CSF-1R was upregulated podocytes biopsies from patients FSGS. Through vitro studies, were constitutively express CSF-1R. Incubation CSF-1 induced upregulation significant transcriptional regulation of genes involved pathways associated activation. Specifically, CSF-1/CSF-1R the ERK1/2 signaling pathway CD44 PECs, while both ERK inhibitors reduced expression. Functional studies showed proliferation migration, reducing differentiation into podocytes. These results validated Adriamycin-induced FSGS experimental mouse model. Importantly, treatment either CSF-1R-specific inhibitor GW2580 or Ki20227 provided robust therapeutic effect. Thus, provide evidence FSGS, paving way for future clinical investigating effect

Language: Английский

Citations

2
How Stem and Progenitor Cells Can Affect Renal Diseases DOI Creative Commons
Francesca Montenegro, Francesca Giannuzzi, Angela Picerno

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(17), P. 1460 - 1460

Published: Aug. 30, 2024

Stem and progenitor cells have been observed to contribute regenerative processes in acute renal failure chronic kidney disease. Recent research has delved into the intricate mechanisms by which stem exert their influence on diseases. Understanding how these integrate with existing architecture response injury could pave way for innovative treatment strategies aimed at promoting repair regeneration. Overall, role of diseases is multifaceted, ability tissue regeneration, immune modulation, maintenance homeostasis. Here, we review studies that available today about involvement both therapies causes diseases, as well natural healing mechanisms, taking account main disorders, such IgA nephropathy, lupus nephritis, diabetic C3 glomerulopathy, focal segmental glomerulosclerosis, idiopathic membranous anti-glomerular basement membrane glomerulonephritis, ANCA-associated crescentic glomerulonephritis. Moreover, based comprehensive data framework specific progenitors, hypothesize a possible adult progenitors exacerbating or recovering illness.

Language: Английский

Citations

1
Gucy1α1 specifically marks kidney, heart, lung and liver fibroblasts DOI Open Access
Valeria Rudman-Melnick, Davy Vanhoutte, Kaitlynn Stowers

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 15, 2024

Abstract Fibrosis is a common outcome of numerous pathologies, including chronic kidney disease (CKD), progressive renal function deterioration. Current approaches to target activated fibroblasts, key effector contributors fibrotic tissue remodeling, lack specificity. Here, we report Gucy1α1 as specific fibroblast marker. levels significantly increased over the course two clinically relevant murine CKD models and directly correlated with established fibrosis markers. Immunofluorescent (IF) imaging showed that comprehensively labelled cortical medullary quiescent fibroblasts in control throughout injury progression, respectively. Unlike traditionally used markers platelet derived growth factor receptor beta (Pdgfrβ) vimentin (Vim), did not overlap off-target populations such podocytes. Notably, both male female mice. Furthermore, observed elevated GUCY1α1 expression human lung. Studies cardiac liver revealed elevation Pdgfrβ-, Vim- alpha smooth muscle actin (αSma)-expressing paralleling progression resolution. Overall, demonstrate an exclusive marker sexes. Due its multiorgan translational potential, might provide novel promising strategy specifically mechanistically examine fibroblasts.

Language: Английский

Citations

0
Gucy1α1 specifically marks kidney, heart, lung and liver fibroblasts DOI Creative Commons
Valeria Rudman-Melnick, Davy Vanhoutte, Kaitlynn Stowers

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 17, 2024

Abstract Fibrosis is a common outcome of numerous pathologies, including chronic kidney disease (CKD), progressive renal function deterioration. Current approaches to target activated fibroblasts, key effector contributors fibrotic tissue remodeling, lack specificity. Here, we report Gucy1α1 as specific fibroblast marker. levels significantly increased over the course two clinically relevant murine CKD models and directly correlated with established fibrosis markers. Immunofluorescent (IF) imaging showed that comprehensively labelled cortical medullary quiescent fibroblasts in control throughout injury progression, respectively. Unlike traditionally used markers platelet derived growth factor receptor beta (Pdgfrβ) vimentin (Vim), did not overlap off-target populations such podocytes. Notably, both male female mice. Furthermore, observed elevated GUCY1α1 expression human lung. Studies cardiac liver revealed elevation Pdgfrβ-, Vim- alpha smooth muscle actin (αSma)-expressing paralleling progression resolution. Overall, demonstrate an exclusive marker sexes. Due its multiorgan translational potential, might provide novel promising strategy specifically mechanistically examine fibroblasts.

Language: Английский

Citations

0
Single-cell RNA sequencing data locate ALDH1A2-mediated retinoic acid synthetic pathway to glomerular parietal epithelial cells DOI Creative Commons
Wenbin Liu, Damian Fermin, Anlong Xu

et al.

Experimental Biology and Medicine, Journal Year: 2024, Volume and Issue: 249

Published: Sept. 18, 2024

Aldehyde dehydrogenase 1, family member A2, is a retinoic acid-synthesizing enzyme encoded by Aldh1a2 in mice and ALDH1A2 humans. This indispensable for kidney development, but its role physiology pathophysiology remains to be fully defined. In this review, we mined single-cell single-nucleus RNA sequencing databases of mouse human kidneys found that glomerular parietal epithelial cells (PECs) express full set genes encoding proteins needed cellular vitamin A uptake, intracellular transport, metabolism into acid. particular, Aldh1a2/ALDH1A2 mRNAs are selectively enriched PECs. expression PECs greatly increased model anti-glomerular basement membrane glomerulonephritis moderately induced ischemia-reperfusion acute injury. substantially repressed chronic disease combining diabetes, hypertension, partial nephrectomy models focal segmental glomerulosclerosis diabetic nephropathy. Single-nucleus data show mRNA diminished patients with associated hypertension polycystic disease. addition mining, also performed Spearman’s rank correlation coefficient analyses identified gene transcripts correlated PEC subtypes, healthy subjects AKI or CKD. Furthermore, conducted Gene Ontology pathway the biological pathways among these -correlated genes. Our mining led us hypothesize - mediated acid synthesis plays yet-undefined dysregulation mediates Conditional, PEC-selective knockout, silencing transgenic will useful tools test hypothesis. Clinical studies on genetics, epigenetics, functions other biosynthesis signaling warranted.

Language: Английский

Citations

0
Gucy1α1 specifically marks kidney, heart, lung and liver fibroblasts DOI Creative Commons
Valeria Rudman-Melnick, Davy Vanhoutte, Kaitlynn Stowers

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 26, 2024

Fibrosis is a common outcome of numerous pathologies, including chronic kidney disease (CKD), progressive renal function deterioration. Current approaches to target activated fibroblasts, key effector contributors fibrotic tissue remodeling, lack specificity. Here, we report Gucy1α1 as specific fibroblast marker. levels significantly increased over the course two clinically relevant murine CKD models and directly correlated with established fibrosis markers. Immunofluorescent (IF) imaging showed that comprehensively labelled cortical medullary quiescent fibroblasts in control throughout injury progression, respectively. Unlike traditionally used markers platelet derived growth factor receptor beta (Pdgfrβ) vimentin (Vim), did not overlap off-target populations such podocytes. Notably, both male female mice. Furthermore, observed elevated GUCY1α1 expression human lung. Studies cardiac liver revealed elevation Pdgfrβ-, Vim- alpha smooth muscle actin (αSma)-expressing paralleling progression resolution. Overall, demonstrate an exclusive marker sexes. Due its multiorgan translational potential, might provide novel promising strategy specifically mechanistically examine fibroblasts.

Language: Английский

Citations

0
PDGF-D Is Dispensable for the Development and Progression of Murine Alport Syndrome DOI

Emilia Anouk Margo Firat,

Eva Miriam Buhl, Nassim Bouteldja

et al.

American Journal Of Pathology, Journal Year: 2024, Volume and Issue: 194(5), P. 641 - 655

Published: Feb. 1, 2024

Language: Английский

Citations

0
Identification of Immune-Related Genes as Biomarkers for Uremia DOI Creative Commons

Dongning Lyu,

Guangyu He,

Kan Zhou

et al.

International Journal of General Medicine, Journal Year: 2023, Volume and Issue: Volume 16, P. 5633 - 5649

Published: Nov. 1, 2023

Uremia, which is characterized by immunodeficiency, associated with the deterioration of kidney function. Immune-related genes (IRGs) are crucial for uremia progression.The co-expression network was constructed to identify key modular uremia. IRGs were intersected differentially expressed (DEGs) between and control groups obtain (DEIRGs). DEIRGs subjected functional enrichment analysis. The protein-protein interaction (PPI) constructed. candidate identified using cytoHubba tool. biomarkers various machine learning algorithms. diagnostic value evaluated receiver operating characteristic (ROC) immune infiltration analysis implemented. biological pathways gene set ingenuity pathway mRNA expression validated blood samples patients healthy subjects quantitative real-time polymerase chain reaction (qRT-PCR).In total, four (PDCD1, NGF, PDGFRB, ZAP70) methods. ROC demonstrated that area under curve values individual > 0.9, indicating good power. nomogram model exhibited predictive proportions six cells significantly varied groups. ZAP70 positively correlated resting natural killer (NK) cells, naïve B regulatory T cells. Functional revealed mainly translational function neuroactive ligand-receptor interaction. regulated NK cell signaling. PDCD1 NGF levels determined qRT-PCR consistent those bioinformatics analysis.PDCD1, as uremia, providing a theoretical foundation diagnosis.

Language: Английский

Citations

0