Epithelial to Mesenchymal Transition (EMT) and Endothelial to Mesenchymal Transition (EndMT): Role and Implications in Kidney Fibrosis

Cruz-Solbes, A.S.; Youker, Keith A.

doi:10.1007/978-3-319-51436-9_13

Cited by 105 publications

(92 citation statements)

References 101 publications

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“…This proposed pathway requires further characterisation. TGF-β is described as the major regulator of EndMT and harbours profibrotic properties by inducing and propagating resident fibroblasts [59]. As TGF-β1 mediates both Smad- Fig.…”

Section: Discussionmentioning

confidence: 99%

lncRNA H19 prevents endothelial–mesenchymal transition in diabetic retinopathy

et al. 2019

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Aims/hypothesis The pathophysiology of diabetic retinopathy is linked to hyperglycaemia and its effect on retinal microvascular tissues. The resulting endothelial injury changes the endothelial cell phenotype to acquire mesenchymal properties (i.e. endothelial-mesenchymal transition [EndMT]). Such changes can be regulated by epigenetic mechanisms, including long non-coding RNAs (lncRNAs). lncRNA H19 may influence EndMT through TGF-β. We investigated the role of H19 in regulating EndMT during diabetic retinopathy. Methods H19 was overexpressed or silenced in human retinal endothelial cells exposed to various glucose levels. The cells were examined for H19, endothelial and mesenchymal markers. We then expanded the study to retinal tissues in a mouse model of diabetic retinopathy and also examined vitreous humour samples from individuals with proliferative diabetic retinopathy. Results Expression of H19 was downregulated in high glucose conditions (25 mmol/l). H19 overexpression prevented glucoseinduced EndMT. Such changes appear to involve TGF-β through a Smad-independent mechanism. Diabetes caused downregulation of retinal H19. Using H19 knockout mice, we demonstrated similar EndMT in the retina. Examination of vitreous humour from individuals with proliferative diabetic retinopathy also reinforced the downregulation of H19 in diabetes. Conclusions/interpretationWe therefore concluded that H19 regulates EndMT in diabetic retinopathy through specific mechanisms. Data availability The results from our previous microarray can be found online using the GEO accession number GSE122189.

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Section: Discussionmentioning

confidence: 99%

lncRNA H19 prevents endothelial–mesenchymal transition in diabetic retinopathy

et al. 2019

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“…Other types of transition programs contribute to the fibroblast pool in tissue fibrosis and tumors, including EndMT, pericyte and adipocyte‐to‐fibroblast transitions . With respect to the perivascular source of fibroblasts, it should also be noted that large blood vessels contain perivascular fibroblasts (Table ) along the outermost layer (vascular adventitia), and are also referred to as adventitial fibroblasts .…”

Section: Molecular and Functional Characteristics Of Fibroblastsmentioning

confidence: 99%

Origin and functional heterogeneity of fibroblasts

2020

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The inherent plasticity and resiliency of fibroblasts make this cell type a conventional tool for basic research. But where do they come from, are all fibroblasts the same, and how do they function in disease? The first fibroblast lineages in mammalian development emerge from the ooze of primary mesenchyme during gastrulation. They are cells that efficiently create and negotiate the extracellular matrix of the mesoderm in order to migrate and meet their developmental fate. Mature fibroblasts in epithelial tissues live in the interstitial spaces between basement membranes that spatially delimit complex organ structures. While the function of resident fibroblasts in healthy tissues is largely conjecture, the accumulation of fibroblasts in pathologic lesions offers insight into biologic mechanisms that control their function; fibroblasts are poised to coordinate fibrogenesis in tissue injury, neoplasia, and aging. Here, we examine the developmental origin and plasticity of fibroblasts, their molecular and functional definitions, the epigenetic control underlying their identity and activation, and the evolution of their immune regulatory functions. These topics are reviewed through the lens of fate mapping using genetically engineered mouse models and from the perspective of single‐cell RNA sequencing. Recent observations suggest dynamic and heterogeneous functions for fibroblasts that underscore their complex molecular signatures and utility in injured tissues.

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“…More specifically, renal tubular epithelial cells (RTECs) undergo stepwise loss of inherent epithelial markers, such as E-cadherin, and acquire the characteristics of mesenchymal cells including the expression of mesenchymal markers, such as vimentin and a-smooth muscle actin (a-SMA) and enhance mobility. Those cells then traverse the tubular basement membrane (TBM) into the renal interstitium, which causes excessive deposition of ECM, leading to fibrosis (Yang and Liu, 2001;Cruz-Solbes and Youker, 2017). Moreover, a vast variety of stimuli of the renal tubular EMT, such as hypoxia (Higgins et al, 2007), ischemia/reperfusion (Chen et al, 2017b), proteinuria (Efstratiadis et al, 2009), and cytokines-particularly TGF-b (Sutariya et al, 2016) and MMPs (Du et al, 2012), etc.…”

Section: Introductionmentioning

confidence: 99%

Protective effect of retinoic acid receptor α on hypoxia‐induced epithelial to mesenchymal transition of renal tubular epithelial cells associated with TGF‐β/MMP‐9 pathway

Gong

Jiang

Qin

et al. 2018

Cell Biology International

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Retinoic acid receptor α (RARα), a member of family of the nuclear retinoic acid receptors (RARs), plays an essential role in various chronic kidney diseases (CKD). Renal tubular epithelial to mesenchymal transition (EMT) is a common mechanism of progression of renal interstitial fibrosis (RIF). Hypoxia has been extensively considered as one of major inducers of renal tubular EMT. However, the effects of RARα on hypoxia-induced EMT have not yet been described so far. The aim of the present study was to explore the roles and potential mechanisms of RARα in hypoxia-induced EMT of renal tubular epithelial cells (RTECs). Our results showed that expression of RARα in RTECs subjected to hypoxia significantly was reduced, accompanied by decreased expression level of the epithelial marker E-cadherin, and increased expression levels of the mesenchymal markers α-smooth muscle actin (α-SMA) and vimentin, in accord with EMT. Meanwhile, hypoxia could cause RTECs to obviously express TGF-β and matrix metalloproteinase-9 (MMP-9). Furthermore, using lentivirus-based delivery vectors to overexpress RARα in RTECs, we demonstrated that RARα alleviated hypoxia-induced EMT of RTECs and downregulated the expression levels of TGF-β and MMP-9. In a word, RARα protects RTECs against EMT induced by hypoxia associated with TGF-β/MMP-9 pathway.

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Epithelial to Mesenchymal Transition (EMT) and Endothelial to Mesenchymal Transition (EndMT): Role and Implications in Kidney Fibrosis

Cited by 105 publications

References 101 publications

lncRNA H19 prevents endothelial–mesenchymal transition in diabetic retinopathy

lncRNA H19 prevents endothelial–mesenchymal transition in diabetic retinopathy

Origin and functional heterogeneity of fibroblasts

Protective effect of retinoic acid receptor α on hypoxia‐induced epithelial to mesenchymal transition of renal tubular epithelial cells associated with TGF‐β/MMP‐9 pathway

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