The role of EMT in renal fibrosis

Carew, Rosemarie M.; Wang, Bo; Kantharidis, Phillip

doi:10.1007/s00441-011-1227-1

Cited by 258 publications

(205 citation statements)

References 177 publications

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“…The origin of these collagen-forming cells is not always clear, but it has classically been accepted that they derive from tissue-resident fibroblasts; recent evidence suggests that other cell populations (i.e., organ epithelial cells) are also able to generate MFB during EMT induction. Moreover, it is clear that type 2 EMT of epithelial cells from organs undergoing fibrosis results in the ability to produce ECM components [121,122]. For example, MFB in the liver mainly originates from the activation of hepatic stellate cells (HSC) [119]; however, adult hepatocytes that undergo EMT induced by TGF-β can also contribute to the MFB population [123][124][125].…”

Section: Purinergic Signaling Emt and Fibrosismentioning

confidence: 99%

Nucleotides and nucleoside signaling in the regulation of the epithelium to mesenchymal transition (EMT)

Martinez-Ramirez

Dı́az-Muñoz

Butanda-Ochoa

et al. 2016

Purinergic Signalling

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The epithelium-mesenchymal transition (EMT) is an important process of cell plasticity, consisting in the loss of epithelial identity and the gain of mesenchymal characteristics through the coordinated activity of a highly regulated informational program. Although it was originally described in the embryonic development, an important body of information supports its role in pathology, mainly in cancerous and fibrotic processes. The purinergic system of inter-cellular communication, mainly based in ATP and adenosine acting throughout their specific receptors, has emerged as a potent regulator of the EMT in several pathological entities. In this context, cellular signaling associated to purines is opening the understanding of a new element in the complex regulatory network of this phenotypical differentiation process. In this review, we have summarized recent information about the role of ATP and adenosine in EMT, as a growing field with high therapeutic potential.Keywords P2 receptors . P1 receptors . Purinergic signaling . Cell migration . EMTThe purinergic system of intercellular communication General aspects The term purine (from: pure urine) was created more than 130 years ago by Emil Fischer after detailed analytical characterization of the uric acid molecule [1]. Purine molecular structure is the result of fusing pyrimidine and imidazole rings, and it exists as four N-H tautomeric forms [2]. Tautomerism of purine bases in DNA is one of the earliest reasons for mutations [3][4][5]. The interconversion of the different adenine or guanine tautomers produced mispairing with pyrimidines (which also show tautomeric forms) that may lead to changes in DNA sequence [6].Purine molecules appeared very early in the history of our planet, in the period known as Borganic evolution^, before the establishment of living systems. It has been postulated that purines could be formed by a eutectic (denoting a mixture of substances in fixed proportions that melts and freezes at a single temperature that is lower than the melting points of any of the separate constituents) concentration of HCN at extremely low temperature over a period of dozens of years [7]. Purine molecules, such as adenine and guanine, are components of the genetic material (DNA and RNA) of all living beings. Purine and pyrimidine tautomeric equilibria in nucleic acids was postulated to be significant in events such as DNA replication and repair as well as in the occurrence of point mutations [8].As nucleosides and nucleotides, purines play other highly strategic roles, acting as energy intermediates, allosteric regulators of key metabolic activities, redox molecules, and chemical messengers for signal transduction events. The two most important purines serving as extracellular ligands for paracrine and autocrine signaling are ATP and its dephosphorylated form, adenosine (ADO). ATP and ADO act as intracellular intermediate metabolites, and their presence in the

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Section: Purinergic Signaling Emt and Fibrosismentioning

confidence: 99%

Nucleotides and nucleoside signaling in the regulation of the epithelium to mesenchymal transition (EMT)

Martinez-Ramirez

Dı́az-Muñoz

Butanda-Ochoa

et al. 2016

Purinergic Signalling

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“…9 It is widely accepted in the literature that there are similarities between the development of fi brosis and embryonic morphogenesis, 10 concepts not limited to the lung. 11 Fibulin-1 is produced by lung fi broblasts 12 and has been shown to play a role in the pathophysiology of patients with asthma, 13 a disease characterized in part by airway fi brosis. 14 We reasoned that dysregulated fi bulin-1 expression may be involved in lung diseases with more extensive fi brosis as mechanisms of fi brogenesis are likely to be shared.…”

Section: Fibulin-1 Levels In Tissuementioning

confidence: 99%

Fibulin-1 Predicts Disease Progression in Patients With Idiopathic Pulmonary Fibrosis

Jaffar

Unger

Corte

et al. 2014

CHEST

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BACKGROUND:The underlying mechanisms of idiopathic pulmonary fibrosis (IPF) are unknown. Th is progressive disease has high mortality rates, and current models for prediction of mortality have limited value in identifying which patients will progress. We previously showed that the glycoprotein fi bulin-1 is involved in enhanced proliferation and wound repair by mesenchymal cells and, thus, may contribute to lung fi brosis in IPF.

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“…Hypoxia induces EMT in different kinds of cell. [9][10][11][12] In this study, we found that hypoxia induced EMT in human mesothelial cells (Met-5A cells) and primary-cultured rat peritoneal mesothelial cells. The EMT changes of Met-5A cells were abolished by HIF-1a inhibition.…”

Section: -8mentioning

confidence: 66%

“…[5][6][7][8] Hypoxia contributes to EMT in different kinds of cell, such as malignant cells and renal tubular cells. [9][10][11][12] Hypoxia is also associated with end-stage renal disease, and is a risk factor for cardiovascular events. [13][14][15] However, its roles in the EMT of peritoneal mesothelial cells have not been fully clarified.…”

Section: Introductionmentioning

confidence: 99%

HIF-1α mediates Hypoxia-induced epithelial–mesenchymal transition in peritoneal mesothelial cells

et al. 2015

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The epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells plays a pivotal role in the development of peritoneal fibrosis. The pathological effects of hypoxia on mesothelial cell EMT have not been fully elucidated. In this study, we, therefore, investigated the effects of hypoxia on EMT in mesothelial cells. Human mesothelial (MeT-5A) cells and primary-cultured rat mesothelial cells were cultured under hypoxic conditions (1% O 2 ) for up to 72 h. Changes in cell type were then determined by investigating changes in morphology and in expression of epithelial (E-cadherin and occludin) and mesenchymal (fibronectin-1, vimentin and a-smooth muscle actin) cell markers. In some cases, MeT-5A cells were cultured under hypoxic conditions with a HIF-1a inhibitor and then assessed for changes in morphology and for altered expression of signaling molecules, such as HIF-1a, Snail-1, vascular endothelial growth factor (VEGF), and matrix metalloproteinase-2 (MMP-2). Levels of HIF-1a, Snail-1, VEGF, and MMP-2 in Met-5A cells were increased by hypoxia. Levels of epithelial cell markers were decreased and those of mesenchymal cell markers were increased. Cell morphology also changed from a cobblestone-like monolayer to spindle-shaped fibroblast-like cells in response to hypoxia. Inhibition of HIF-1a signaling by a HIF-1a inhibitor abrogated these changes. The cell marker and morphological changes induced by hypoxia were also observed in primary-cultured rat mesothelial cells. We can conclude that hypoxia induces EMT in mesothelial cells by activating HIF-1a. This finding indicates that hypoxia has pivotal roles in the development of peritoneal fibrosis in peritoneal dialysis patients. ARTICLE HISTORY

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The role of EMT in renal fibrosis

Cited by 258 publications

References 177 publications

Nucleotides and nucleoside signaling in the regulation of the epithelium to mesenchymal transition (EMT)

Nucleotides and nucleoside signaling in the regulation of the epithelium to mesenchymal transition (EMT)

Fibulin-1 Predicts Disease Progression in Patients With Idiopathic Pulmonary Fibrosis

HIF-1α mediates Hypoxia-induced epithelial–mesenchymal transition in peritoneal mesothelial cells

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