Molecular Mechanisms of TGF-β Signaling in Renal Fibrosis

Chung, Arthur C.K.; Lan, Hui Y.

doi:10.1007/s40139-013-0027-6

Cited by 9 publications

(8 citation statements)

References 97 publications

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“…Activin A and TGFB2 are involved in the formation of the ureteric bud [100,101] while TGFB2 knock-out results in kidney agenesis in mice [102]. TGF-β is a critical mediator of renal fibrosis by promoting intense production and accumulation of components of the extracellular matrix (ECM), resulting in renal damage [103]. Renal fibrosis contributes to development of chronic kidney diseases (CKDs), which in turn may progress to end-stage renal diseases (ESRDs).…”

Section: Renal Cancermentioning

confidence: 99%

TGF-β and microRNA Interplay in Genitourinary Cancers

Bogusławska¹,

Kryst

Poletajew

et al. 2019

Cells

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Genitourinary cancers (GCs) include a large group of different types of tumors localizing to the kidney, bladder, prostate, testis, and penis. Despite highly divergent molecular patterns, most GCs share commonly disturbed signaling pathways that involve the activity of TGF-β (transforming growth factor beta). TGF-β is a pleiotropic cytokine that regulates key cancer-related molecular and cellular processes, including proliferation, migration, invasion, apoptosis, and chemoresistance. The understanding of the mechanisms of TGF-β actions in cancer is hindered by the “TGF-β paradox” in which early stages of cancerogenic process are suppressed by TGF-β while advanced stages are stimulated by its activity. A growing body of evidence suggests that these paradoxical TGF-β actions could result from the interplay with microRNAs: Short, non-coding RNAs that regulate gene expression by binding to target transcripts and inducing mRNA degradation or inhibition of translation. Here, we discuss the current knowledge of TGF-β signaling in GCs. Importantly, TGF-β signaling and microRNA-mediated regulation of gene expression often act in complicated feedback circuits that involve other crucial regulators of cancer progression (e.g., androgen receptor). Furthermore, recently published in vitro and in vivo studies clearly indicate that the interplay between microRNAs and the TGF-β signaling pathway offers new potential treatment options for GC patients.

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Section: Renal Cancermentioning

confidence: 99%

TGF-β and microRNA Interplay in Genitourinary Cancers

Bogusławska¹,

Kryst

Poletajew

et al. 2019

Cells

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“…Previously, tremendous evidence has revealed that TGFβ is substantially upregulated in renal fibrosis, and overexpression of active TGF-β is capable of inducing renal fibrosis [4,6]. In contrast, blocking TGF-β using a neutralizing antibody, antisense oligonucleotides, inhibitors, or genetic deletion of receptors effectively alleviates the degree of renal fibrosis both in vivo and in vitro [7].…”

Section: Introductionmentioning

confidence: 99%

miR-155-5p Implicates in the Pathogenesis of Renal Fibrosis via Targeting SOCS1 and SOCS6

Zhang

Tang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Renal fibrosis is associated with the reduction in the functional renal parenchyma and in most cases progresses to end-stage kidney failure, a devastating condition that requires lifelong dialysis or kidney transplantation. However, due to the extreme complexity in the pathogenesis of renal fibrosis and our limited knowledge, therapeutic options for renal fibrosis in the clinical setting are still scarce and often ineffective. Hence, further studies on the molecular mechanisms underlying renal fibrosis are compellingly needed. Multiple miRNAs have demonstrated to participate in kidney diseases in a TGF-β dependent or independent manner, but there is very little known about miR-155-5p on renal fibrosis. In the present study, we firstly explored the expression level and functions of miR-155-5p in the setting of renal fibrosis. Our research revealed that miR-155-5p is highly expressed in kidney tissues from patients and unilateral ureteral obstruction (UUO) rat models, and miR-155-5p knockdown significantly blocks renal fibrosis both in vivo and in vitro. In mechanism, our data demonstrate that miR-155-5p promotes renal fibrosis by increasing the phosphorylated activation of STAT3 via targeting SOCS1/6. Altogether, our findings highlight a miR-155-5p/SOCS/STAT3 axis in the pathogenesis of renal fibrosis, which may provide promising therapeutic targets for clinical prevention of this disease.

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“…Renal fibrosis covers four overlapping stages: The fibrogenic stage, activation, expansion and progression (2). Transforming growth factor-β (TGF-β) signaling is the important mediator in the progression of renal fibrosis via inducing the extracellular matrix to form renal scarring (3). Mitogen-activated protein kinase (MAPK) serves a role in the extracellular matrix in renal fibrosis as being downstream of TGFβ (4).…”

Section: Introductionmentioning

confidence: 99%

Potential role of upregulated microRNA-146b and −21 in renal fibrosis

Xin

Zhou

Zhang

et al. 2017

Molecular Medicine Reports

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The aim of the present study was to identify candidate microRNAs (miRNAs) involved in the progression of renal fibrosis. Dataset GSE42716 of miRNAs extracted from kidneys from mice with unilateral ureteral obstruction (UUO), and mice without UUO was downloaded from the Gene Expression Omnibus database. The Limma package was used to identify differential expression between mice with and without UUO. Renal disease‑related miRNAs were predicted based on the miRWalk database. Thereafter, candidate miRNAs were screened by taking the intersection of differentially expressed miRNAs and predicted miRNAs, followed by screening of target genes using miRWalk and transcription factors using the TransmiR database. An integrative regulatory network was constructed using Cytoscape software. Enrichment analysis of target genes was also performed. In total, 76 differentially expressed miRNAs were identified in kidneys with UUO compared with the normal samples based on dataset and 9 miRNAs were identified as related to renal disease from the miRWalk database. A Venn diagram revealed two overlapping upregulated miRNAs; miR‑146b and miR‑21. Transcription factor NFKB1 may activate miR‑146b and AKT may activate miR‑21. In addition, miR‑21 had a regulatory effect on IFNG expression and miR‑146b may regulate the expression of BCL2, PTEN and IFNG. Furthermore, target genes of miR‑146b and miR‑21 were significantly enriched in 14 Gene Ontology terms including regulation of cell proliferation (e.g., BCL2, PTEN and IFNG). Overexpression of miR‑21 may be activated by AKT2 and contribute to renal fibrosis by negatively regulating IFNG expression. Furthermore, miR‑146b may be activated by NFKB1 and subsequently reduce the expression of BCL2, PTEN and IFNG in the progression of renal fibrosis.

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Molecular Mechanisms of TGF-β Signaling in Renal Fibrosis

Cited by 9 publications

References 97 publications

TGF-β and microRNA Interplay in Genitourinary Cancers

TGF-β and microRNA Interplay in Genitourinary Cancers

miR-155-5p Implicates in the Pathogenesis of Renal Fibrosis via Targeting SOCS1 and SOCS6

Potential role of upregulated microRNA-146b and −21 in renal fibrosis

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