Biomarkers of cardio-renal syndrome in uremic myocardiopathy animal model

Dionísio, Laura Mattana; Luvizoto, Mateus Justi; Gribner, Caroline; Carneiro, Danielle; Carvalho, Viviane de Souza Correia de; Robes, Franciele; Sheidemantel, Marcos; Rego, Fabiane Gomes de Moraes; Noronha, Lúcia de; Pécoits-Filho, Roberto; Hauser, Aline Borsato

doi:10.1590/2175-8239-jbn-3878

Cited by 6 publications

(3 citation statements)

References 36 publications

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“…1b ) were also detected in 5/6Nx wild-type mice. Inflammatory cytokines and fibrosis-related factors underlie CKD-induced heart failure 33 , 34 . The mRNA levels of inflammatory cytokines interleukin-6 ( IL-6 ) and tumor necrosis factor-α ( Tnf α) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Alteration of circadian machinery in monocytes underlies chronic kidney disease-associated cardiac inflammation and fibrosis

et al. 2021

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Dysfunction of the circadian clock has been implicated in the pathogenesis of cardiovascular disease. The CLOCK protein is a core molecular component of the circadian oscillator, so that mice with a mutated Clock gene (Clk/Clk) exhibit abnormal rhythms in numerous physiological processes. However, here we report that chronic kidney disease (CKD)-induced cardiac inflammation and fibrosis are attenuated in Clk/Clk mice even though they have high blood pressure and increased serum angiotensin II levels. A search for the underlying cause of the attenuation of heart disorder in Clk/Clk mice with 5/6 nephrectomy (5/6Nx) led to identification of the monocytic expression of G protein-coupled receptor 68 (GPR68) as a risk factor of CKD-induced inflammation and fibrosis of heart. 5/6Nx induces the expression of GPR68 in circulating monocytes via altered CLOCK activation by increasing serum levels of retinol and its binding protein (RBP4). The high-GPR68-expressing monocytes have increased potential for producing inflammatory cytokines, and their cardiac infiltration under CKD conditions exacerbates inflammation and fibrosis of heart. Serum retinol and RBP4 levels in CKD patients are also sufficient to induce the expression of GPR68 in human monocytes. Our present study reveals an uncovered role of monocytic clock genes in CKD-induced heart failure.

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Section: Resultsmentioning

confidence: 99%

Alteration of circadian machinery in monocytes underlies chronic kidney disease-associated cardiac inflammation and fibrosis

et al. 2021

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“…The 5/6 nephrectomy was operated according routine protocol. 12 In sham-operated animals, only renal pedicle was just detached. At fifth week after subtotal nephrectomy, ICG-001 (#847591-62-2; Chembest, Shanghai, China) were administered to rats with daily intraperitoneal injection, at dosage of 5 mg/kg body weight for additional 4 weeks.…”

Section: Animal Modelsmentioning

confidence: 99%

Wnt/β‐catenin signalling mediates cardiac hypertrophy in type 4 cardiorenal syndrome

Zhao

Lei

et al. 2021

Nephrology

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Aim: Cardiorenal syndrome type 4 (CRS4) is characterized by the condition that chronic kidney disease (CKD) causes sustainable injury to heart. This study focuses on exploring the mechanism underlying CRS4 and potential treatment for CRS4.Methods: In the present study, Sprague Dawley (SD) rats were subjected to 5/6 subtotal nephrectomy (5/6NX) for generating animal model of CKD. Cardiac hypertrophy, kidney injury, Wnt/β-catenin signalling and serum TNF-α were tested at eighth week after 5/6NX.Results: Cardiac hypertrophy and kidney injury were prominent and accompanied by Wnt/β-catenin activation in rats at eighth week after 5/6NX. Blockade of Wnt/βcatenin by ICG-001 reduced 5/6NX-stimulated fibronectin and podocalyxin in remnant kidney. Interestingly, ICG-001 also inhibited hypertrophic markers β-MHC and α-actin and reduced cardiac hypertrophy. In addition, TNF-α, as a systemic inflammation factor in blood circulation, was suggested to connect CKD to cardiac hypertrophy. It was demonstrated in vitro and in vivo studies that ICG-001 is sufficient to counteract TNF-α-induced cardiac hypertrophy by sequestration of β-catenin. Conclusion:These results demonstrate that Wnt/β-catenin to be a unified pathogenic pathway of heart disorder and kidney disease in CRS4. Based on that, Wnt/βcatenin signalling could be a target of promising therapy for protecting both heart and kidney organs in CRS4.

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“…For instance, in sepsis-induced acute CRS-5, there is a fulminant disease process that has a dramatic impact on both the kidneys and heart [ 19 ]. The microarray data profiling of sepsis, CRS, and SLE, and extensive gene techniques, have been used to identify differentially expressed genes (DEGs) [ 20 , 21 , 22 , 23 ]. Incorporating, integrating, and re-analyzing existing data using bioinformatics tools can provide new strategies, methods, and relevant information.…”

Section: Introductionmentioning

confidence: 99%

Identification and Validation of Pathogenic Genes in Sepsis and Associated Diseases by Integrated Bioinformatics Approach

Ahmed

Zaki

Alhazmi

et al. 2022

Genes

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Sepsis is a clinical syndrome with high mortality and morbidity rates. In sepsis, the abrupt release of cytokines by the innate immune system may cause multiorgan failure, leading to septic shock and associated complications. In the presence of a number of systemic disorders, such as sepsis, infections, diabetes, and systemic lupus erythematosus (SLE), cardiorenal syndrome (CRS) type 5 is defined by concomitant cardiac and renal dysfunctions Thus, our study suggests that certain mRNAs and unexplored pathways may pave a way to unravel critical therapeutic targets in three debilitating and interrelated illnesses, namely, sepsis, SLE, and CRS. Sepsis, SLE, and CRS are closely interrelated complex diseases likely sharing an overlapping pathogenesis caused by erroneous gene network activities. We sought to identify the shared gene networks and the key genes for sepsis, SLE, and CRS by completing an integrative analysis. Initially, 868 DEGs were identified in 16 GSE datasets. Based on degree centrality, 27 hub genes were revealed. The gProfiler webtool was used to perform functional annotations and enriched molecular pathway analyses. Finally, core hub genes (EGR1, MMP9, and CD44) were validated using RT-PCR analysis. Our comprehensive multiplex network approach to hub gene discovery is effective, as evidenced by the findings. This work provides a novel research path for a new research direction in multi-omics biological data analysis.

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Biomarkers of cardio-renal syndrome in uremic myocardiopathy animal model

Cited by 6 publications

References 36 publications

Alteration of circadian machinery in monocytes underlies chronic kidney disease-associated cardiac inflammation and fibrosis

Alteration of circadian machinery in monocytes underlies chronic kidney disease-associated cardiac inflammation and fibrosis

Wnt/β‐catenin signalling mediates cardiac hypertrophy in type 4 cardiorenal syndrome

Identification and Validation of Pathogenic Genes in Sepsis and Associated Diseases by Integrated Bioinformatics Approach

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