Screening and functional analysis of differentially expressed genes in chronic glomerulonephritis by whole genome microarray

Gao, Jiarong; Qin, Xiujuan; Jiang, Hui; Wang, Ting; Jun-mei, Song; Shuangzhi, Xu

doi:10.1016/j.gene.2016.05.031

Cited by 18 publications

(17 citation statements)

References 34 publications

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“…On the other hand, leukocyte transendothelial migration and natural killer cell-mediated cytotoxicity might be related with the renal injury. As reported, Itgb7 was the marker of renal inflammation [32,34]. Though without histological change, kidney might suffer from inflammation at the early stage of acute liver injury.…”

Section: Discussionmentioning

confidence: 78%

“…In our study, despite no renal histological changes were observed in BDL and LR models, the renal transcriptomic changes were significant in these two models. Among the 18 genes co-upregulated in BDL and LR models, Fyb, Sfrp2, Hic1, Itgb7, and Esm1 were reported to participate in renal development or diseases [29][30][31][32][33][34]. The 18 genes upregulated simultaneously in these two models were enriched in focal adhesion related pathways.…”

Section: Discussionmentioning

confidence: 97%

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Potential Crosstalk between Liver and Extra-liver Organs in Mouse Models of Acute Liver Injury

et al. 2020

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Carbon tetrachloride (CCl4), Concanavalin A (ConA), bile duct ligation (BDL), and liver resection (LR) are four types of commonly used mouse models of acute liver injury. However, these four models belong to different types of liver cell damage while their application situations are often confounded. In addition, the systematic changes of multiple extra-liver organs after acute liver injury and the crosstalk between liver and extra-liver organs remain unclear. Here, we aim to map the morphological, metabolomic and transcriptomic changes systematically after acute liver injury and search for the potential crosstalk between the liver and the extra-liver organs. Significant changes of transcriptome were observed in multiple extra-liver organs after different types of acute liver injury despite dramatic morphological damage only occurred in lung tissues of the ConA/BDL models and spleen tissues in the ConA model. Liver transcriptomic changes initiated the serum metabolomic alterations which correlated to transcriptomic variation in lung, kidney, and brain tissues of BDL and LR models. The potential crosstalk might lead to pulmonary damage and development of hepatorenal syndrome (HRS) and hepatic encephalopathy (HE) during liver injury. Serum derived from acute liver injury mice damaged alveolar epithelial cells and human podocytes in vitro. Our data indicated that different types of acute liver injury led to different transcriptomic changes within extra-liver organs. Integration of serum metabolomics and transcriptomics from multiple tissues can improve our understanding of acute liver injury and its effect on the other organs.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 97%

Potential Crosstalk between Liver and Extra-liver Organs in Mouse Models of Acute Liver Injury

et al. 2020

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“…In the current study, ADR-induced CGN rats and LPS-stimulated HBZY-1 cells were used to explore the molecular pathogenesis of CGN ( 7 ). The results indicated that the kidney viscera index and the 24 h urinary protein, BUN and Crn levels were significantly increased while body weight decreased.…”

Section: Discussionmentioning

confidence: 99%

“…Following acclimatization for 2 weeks, all animals were divided randomly into the control group and experimental model group (n=10 per group). CGN was induced in the rats by tail intravenous injection with ADR: 3.5 mg/kg ADR was given on the 1st day and 3.0 mg/kg on the 14th day ( 7 , 14 ), whereas the control group was administered a saline solution for comparison at the same time. On the 21st day, all rats were placed into metabolism cages and urine was collected over 24 h to determine the urinary protein levels.…”

Section: Methodsmentioning

confidence: 99%

“…In the authors previous experiments, differentially regulated genes were screened and analyzed. The results revealed that Fos and spleen-associated tyrosine kinase (Syk) were potent hub genes and that CGN pathogenesis may be associated with the disordered inflammatory response in addition to abnormal metabolism ( 7 ). Therefore, it is important to explain the specific mechanism of Fos and Syk in CGN, which may contribute to understanding the pathogenesis of CGN and developing novel diagnostic markers.…”

Section: Introductionmentioning

confidence: 99%

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In�vitro and in�vivo study of the expression of the Syk/Ras/c‑Fos pathway in chronic glomerulonephritis

et al. 2018

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Chronic glomerulonephritis (CGN) is the most common form of glomerular disease; however, its associated molecular mechanisms remain unclear. Spleen tyrosine kinase (Syk) is a key mediator of B-receptor signaling on the surface of inflammatory cells. The primary target for R406 is Syk. The aim of the present study was to investigate the molecular mechanisms involved in a rat model of CGN induced by adriamycin (ADR) and in the rat glomerular mesangial cell line, HBZY-1, stimulated by lipopolysaccharide (LPS). CGN was induced in the rat models by two intravenous injections of ADR into the tail: 3.5 mg/kg ADR was given on the first day and 3.0 mg/kg on the fourteenth day. HBZY-1 cells were incubated with 0.5 µg/ml LPS for 48 h. The pathological alterations in the kidney tissues were observed by hematoxylin and eosin staining. The 24 h urinary protein, blood urea nitrogen (BUN) and creatinine levels were measured using an automatic biochemistry analyzer. The mRNA expression levels of Syk, Ras, mitogen activated protein kinase kinase (MEK), extracellular signal regulated kinase (ERK)1/2 and c-Fos was measured by reverse transcription-quantitative polymerase chain reaction. Subsequently, the protein levels of phosphorylated (p)-Syk, Ras, p-MEK1/2, p-ERK1/2 and c-Fos were measured by western blot analysis. In the model group, 24 h urinary protein, BUN and creatinine levels were increased when compared with the normal group (P<0.05). In addition, compared with the normal group, the mRNA and protein levels of the Syk/Ras/c-Fos pathway components in vitro and in vivo were markedly increased, inhibiting the abnormal cell viability of mesangial cells. In conclusion, the results of the present study suggested a potential role for the Syk/Ras/c-Fos signaling pathway in CGN, which indicated the necessity for further investigation at the clinical level.

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Runt‐related transcription factor 1 (RUNX1) is a mediator of acute kidney injury

Fontecha‐Barriuso,

Villar‐Gomez,

Guerrero‐Mauvecin

et al. 2024

The Journal of Pathology

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Treatment for acute kidney injury (AKI) is suboptimal. A better understanding of the pathogenesis of AKI may lead to new therapeutic approaches. Kidney transcriptomics of folic acid‐induced AKI (FA‐AKI) in mice identified Runx1 as the most upregulated RUNX family gene. We then examined the expression of RUNX1 in FA‐AKI, in bacterial lipopolysaccharide (LPS)‐induced cytokine storm‐AKI (CS‐AKI), and in human AKI. In cultured mouse tubule cells, we explored the expression and role of RUNX1 in response to the cytokine TWEAK or LPS. A chemical inhibitor of RUNX1 (Ro5‐3335) was used in animal models of AKI to test its potential as a therapeutic target. RUNX1 overexpression in FA‐AKI was validated at the mRNA and protein levels and localized mainly to tubule cell nuclei. CS‐AKI also upregulated kidney RUNX1. Increased tubule and interstitial RUNX1 expression were also observed in human AKI. In cultured mouse tubule cells, the pro‐inflammatory cytokine TWEAK and LPS increased RUNX1 and IL‐6 expression. Mechanistically, RUNX1 bound to the Il6 gene promoter and RUNX1 targeting with the chemical inhibitor Ro5‐3335, or a specific small interfering RNA (siRNA), prevented the TWEAK‐ and LPS‐induced upregulation of IL6 through a RUNX1/NFκB1 p50 pathway. In vivo, preventive Ro5‐3335 improved kidney function and reduced inflammation in FA‐AKI and CS‐AKI. However, Ro5‐3335 administration after the insult only improved kidney function in CS‐AKI. Kidney transcriptomics identified inflammatory genes and transcription factor mRNAs such as Yap1 and Trp53 as key targets of Ro5‐3335 in CS‐AKI. In conclusion, RUNX1 contributes to AKI by driving the expression of genes involved in inflammation and represents a novel therapeutic target in AKI. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

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Screening and functional analysis of differentially expressed genes in chronic glomerulonephritis by whole genome microarray

Cited by 18 publications

References 34 publications

Potential Crosstalk between Liver and Extra-liver Organs in Mouse Models of Acute Liver Injury

Potential Crosstalk between Liver and Extra-liver Organs in Mouse Models of Acute Liver Injury

In�vitro and in�vivo study of the expression of the Syk/Ras/c‑Fos pathway in chronic glomerulonephritis

Runt‐related transcription factor 1 (RUNX1) is a mediator of acute kidney injury

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