Nur77 ameliorates age‐related renal tubulointerstitial fibrosis by suppressing the TGF‐β/Smads signaling pathway

Ma, Guojing; Chen, Feng; Liu, Yixuan; Zheng, Lianfang; Jiang, Xuehan; Tian, Huanlian; Wang, Xiaoxun; Song, Xiaoyu; Yu, Yang; Wang, Difei

doi:10.1096/fj.202101332r

Cited by 12 publications

(7 citation statements)

References 43 publications

(82 reference statements)

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“…Wang S et al. showed that JMJD1A/NR4A1 signaling could regulate the progression of renal tubular epithelial interstitial fibrosis in HK-2 cells [ 50 ], and maintenance of NR4A1 may be an effective strategy for blocking renal tubulointerstitial fibrosis and improving renal function in elderly individuals [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Renal tubular gene biomarkers identification based on immune infiltrates in focal segmental glomerulosclerosis

Bai

Zhang

et al. 2022

Renal Failure

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Objective The present study identified novel renal tubular biomarkers that may influence the diagnosis and treatment of focal segmental glomerulosclerosis (FSGS) based on immune infiltration. Methods Three FSGS microarray datasets, GSE108112, GSE133288 and GSE121211, were downloaded from the Gene Expression Omnibus (GEO) database. The R statistical software limma package and the combat function of the sva package were applied for preprocessing and to remove the batch effects. Differentially expressed genes (DEGs) between 120 FSGS and 15 control samples were identified with the limma package. Disease Ontology (DO) pathway enrichment analysis was conducted with statistical R software to search for related diseases. Gene set enrichment analysis (GSEA) was used to interpret the gene expression data and it revealed many common biological pathways. A protein-protein interaction (PPI) network was built using the Search Tool for the Retrieval of Interacting Genes (STRING) database, and hub genes were identified by the Cytoscape (version 3.7.2) plug-in CytoHubba. The plug-in Molecular Complex Detection (MCODE) was used to screen hub modules of the PPI network in Cytoscape, while functional analysis of the hub genes and hub nodes involved in the submodule was performed by ClusterProfiler. The least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) analysis were used to screen characteristic genes and build a logistic regression model. Receiver operating characteristic (ROC) curve analyses were used to investigate the logistic regression model and it was then validated by an external dataset GSE125779, which contained 8 FSGS samples and 8 healthy subjects. Cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) was used to calculate the immune infiltration of FSGS samples. Results We acquired 179 DEGs, 79 genes with downregulated expression (44.1%) and 100 genes with upregulated expression (55.9%), in the FSGS samples. The DEGs were significantly associated with arteriosclerosis, kidney disease and arteriosclerotic cardiovascular disease. GSEA revealed that these gene sets were significantly enriched in allograft rejection signaling pathways and activation of immune response in biological processes. Fifteen genes were demonstrated to be hub genes by PPI, and three submodules were screened by MCODE linked with FSGS. Analysis by machine learning methodologies identified nuclear receptor subfamily 4 group A member 1 (NR4A1) and dual specificity phosphatase 1 (DUSP1) as sensitive tubular renal biomarkers in the diagnosis of FSGS, and they were selected as hub genes, as well as hub nodes which were enriched in the MAPK signaling pathway. Immune cell infiltration analysis revealed that the genetic biomarkers were both correlated with activated mast cells, which may amplify FSGS biological processes. Conclusion ...

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Section: Discussionmentioning

confidence: 99%

Renal tubular gene biomarkers identification based on immune infiltrates in focal segmental glomerulosclerosis

Bai

Zhang

et al. 2022

Renal Failure

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“…The fibrotic effect of TGF-β was identified to be induced through the TGF-β/Smad pathway [ 42 ] due to the association of its high levels with tissue fibrosis [ 43 ]. Transforming growth factor β (TGF-β1) elevation is linked to the severity of renal fibrosis that occurs in the course of injuries caused by diabetes, hypertension, aging, and ischemia [ 44 ]. The urinary TGF-β1 levels are positively correlated with renal fibrosis as it reflects the degree of renal pathology and CKD progression [ 45 ].…”

Section: Reviewmentioning

confidence: 99%

Cytokines' Role in the Pathogenesis and Their Targeting for the Prevention of Frozen Shoulder: A Narrative Review

Al‐Ghamdi¹,

Alyami²,

Althaqafi³

et al. 2023

Cureus

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Frozen shoulder (FS) is a common name for shoulder movement limitation with different degrees of shoulder rigidity and pain. It is characterized by varying developmental courses, different levels of shoulder movement limitation, and background ambiguity due to the multiplicity of its causative factors. Systemic inflammatory cytokines monitoring and restraining is easy to apply, fast to conduct, and needs lower costs compared to invasive methods for frozen shoulder stage evaluation and early controlling of its progress to the stage that necessitates surgical intervention. The aim of this review was to assess the recent findings concerning the role of cytokines in FS pathogenesis and the possibility of preventing or controlling their progress through targeting these cytokines by the new drugs candidates, such as hyaluronan (HA), botulinum toxin type A (BoNT A), Tetrandrine, tumor necrosis factor-stimulated gene-6 (TSG-6), and cannabidiol. Searching the PubMed site, we encountered out of 1608 records, from which 16 original studies were included for the quantitative construction of this systematic review screening of the recent studies to investigate the different FS pathogenic pathways. Most of the scenarios are centered around the inflammatory and fibrotic process triggered by synovial and capsular fibroblast stimulation. This mechanism depends mainly on alarmins cytokines, including thymic stromal lymphopoietin (TSLP), interleukin-33 (IL-33), and interleukin-25 (IL-25), with the stimulation of interleukin-1 α (IL-1α), interleukin-1 β (IL-1β), tumor necrosis alpha (TNF-α), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in a joint capsule. Different pathways of transforming growth factor- β (TGF-β) stimulation, resulting in overexpression of the fibrotic factors as tenascin C (TNC), fibronectin 1, collagen I (COL 1) and collagen III (COL III), and matrix metalloproteinases (MMPs) in the capsular or synovial/capsular fibroblasts. The overall investigation of these studies led us to conclude that the new drug candidates proved their efficiency in controlling the common pathogenesis of the inflammatory and fibrotic pathways of frozen shoulder and therefore represent a prospect for easy and early controlling and efficiently treating this serious disease.

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“…TGF-β1 is a major or predominant isoform involved in fibrosis and the effects of TGF-β2 and TGF-β3 may be partially mediated by TGF-β1. The overexpression of TGF-β1 is causally related to the progression of renal fibrosis caused by aging, diabetes, hypertension, obstruction, ischemia and toxin-induced injury ( Gifford et al, 2021 ; Ma et al, 2022 ). TGF-β1 upregulation has been confirmed in patients and animal models with CKD ( Hu et al, 2018 ).…”

Section: Role Of Tgf-β/smad Signaling Pathway In Tubulointerstitial F...mentioning

confidence: 99%

TGF-β/Smad Signaling Pathway in Tubulointerstitial Fibrosis

Sun

Zhang

et al. 2022

Front. Pharmacol.

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Chronic kidney disease (CKD) was a major public health problem worldwide. Renal fibrosis, especially tubulointerstitial fibrosis, is final manifestation of CKD. Many studies have demonstrated that TGF-β/Smad signaling pathway plays a crucial role in renal fibrosis. Therefore, targeted inhibition of TGF-β/Smad signaling pathway can be used as a potential therapeutic measure for tubulointerstitial fibrosis. At present, a variety of targeting TGF-β1 and its downstream Smad proteins have attracted attention. Natural products used as potential therapeutic strategies for tubulointerstitial fibrosis have the characteristics of acting on multiple targets by multiple components and few side effects. With the continuous research and technique development, more and more molecular mechanisms of natural products have been revealed, and there are many natural products that inhibited tubulointerstitial fibrosis via TGF-β/Smad signaling pathway. This review summarized the role of TGF-β/Smad signaling pathway in tubulointerstitial fibrosis and natural products against tubulointerstitial fibrosis by targeting TGF-β/Smad signaling pathway. Additionally, many challenges and opportunities are presented for inhibiting renal fibrosis in the future.

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Nur77 ameliorates age‐related renal tubulointerstitial fibrosis by suppressing the TGF‐β/Smads signaling pathway

Cited by 12 publications

References 43 publications

Renal tubular gene biomarkers identification based on immune infiltrates in focal segmental glomerulosclerosis

Renal tubular gene biomarkers identification based on immune infiltrates in focal segmental glomerulosclerosis

Cytokines' Role in the Pathogenesis and Their Targeting for the Prevention of Frozen Shoulder: A Narrative Review

TGF-β/Smad Signaling Pathway in Tubulointerstitial Fibrosis

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