Epithelial-to-mesenchymal transition in fibrosis: Collagen type I expression is highly upregulated after EMT, but does not contribute to collagen deposition

Hosper, Nynke A.; Berg, Paul P. van den; Rond, Saskia de; Popa, Eliane R.; Wilmer, Martijn J.; Masereeuw, Rosalinde; Bank, Ruud A.

doi:10.1016/j.yexcr.2013.07.014

Cited by 60 publications

(51 citation statements)

References 36 publications

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“…The same was seen in fresh-frozen cortex and in a previous whole cortex microarray study of 3 hypertensive rat models [31]. Transgelin has been shown to mediate transforming growth factor beta (TGF-β)-induced tissue fibrosis in lung epithelial cells [32], and was upregulated in TGF-β treated renal tubular cells in vitro [33]. Vimentin abundance was three times higher in 2K1C tubuli compared with sham, but was not changed in the fresh-frozen cortex.…”

Section: Discussionsupporting

confidence: 54%

“…Vimentin staining was strong in areas with tubular damage, but also in groups and single cells of healthy looking tubules, while it was negative in tubules from sham rats. Vimentin is a mesenchymal marker, and is upregulated in TGF-β-stimulated proximal tubular cells in vitro [33]. Creatine kinase B-type was increased in both 2K1C tubuli and cortex, and is associated with hypertension and renal tubular sodium retention [34].…”

Section: Discussionmentioning

confidence: 99%

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Proteomic Analysis of Minimally Damaged Renal Tubular Tissue from Two-Kidney-One-Clip Hypertensive Rats Demonstrates Extensive Changes Compared to Tissue from Controls

Finne

Marti

Leh

et al. 2016

Nephron

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Background: Tubular atrophy and interstitial fibrosis mark the final stage in most forms of progressive kidney diseases. Little is known regarding changes in the tubular proteome. In this study, we investigated changes in the tubular proteome of normal or minimally damaged tubular tissue in the non-clipped kidney from rats with two-kidney one-clip (2K1C) hypertension. Methods: Formalin-fixed paraffin-embedded kidney sections from four 2K1C rats with hypertensive kidney damage and 6 sham rats were used. Tubulointerstitial tissue without discernable interstitial expansion or pronounced tubular alterations was microdissected and this was assumed to represent an early stage of chronic tubular damage in 2K1C. Samples were analyzed by mass spectrometry and relative protein abundances were compared between 2K1C and sham. Results: A total of 1,160 proteins were identified with at least 2 unique peptides, allowing for relative quantitation between samples. Among these, 151 proteins were more abundant, and 192 proteins were less abundant in 2K1C compared with sham. Transgelin, vimentin and creatine kinase B-type were among the proteins that were most increased in 2K1C. Ingenuity Pathway Analysis showed increased abundance of proteins related to Rho signaling and protein turnover (eIF2 signaling and protein ubiquitination), and decreased abundance of proteins related to fatty acid β-oxidation. Conclusion: Tubular tissue from normal or minimally damaged hypertensive kidney damage demonstrate extensive proteomic changes with upregulation of pathways associated with progressive kidney damage, such as Rho signaling and protein turnover. Thus, proteomics presents itself to be a promising tool for the discovery of early damage markers from not yet morphologically visible tubular damage.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Minimally Damaged Renal Tubular Tissue from Two-Kidney-One-Clip Hypertensive Rats Demonstrates Extensive Changes Compared to Tissue from Controls

Finne

Marti

Leh

et al. 2016

Nephron

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“…Histological analysis of kidneys showed marked improvement in tubulo-interstitial injury and a trend toward glomerular recovery ( Figure 9C), suggesting that EGFR signaling participates in irreversible late-stage kidney damage. Moreover, erlotinib treatment reduced expression of Ctgf and Col1a1, key factors involved in EMT (38,39), in kidneys of Fcgr2b -/-mice to levels similar to those in Fcgr2b -/-Rhbdf2 -/-mice ( Figure 9E). That erlotinib effectively blocked EGFR signaling was confirmed by decreased phosphorylation of EGFR and ERK1/2 in kidney lysates ( Figure 9F).…”

Section: Rhbdf2mentioning

confidence: 67%

iRhom2 promotes lupus nephritis through TNF-α and EGFR signaling

Qing¹,

Chinenov²,

Redecha³

et al. 2018

Journal of Clinical Investigation

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“…Collective data suggest that the concentration of glucose, as an osmotic agent, in PD solutions has an effect on inducing detrimental histological and ultrastructural alterations within the peritoneum [26]. The hallmark of fibrosis is an accumulation of fibrillar collagens, especially of collagen type I [27], whereas peritoneal thickening may not necessarily be associated with fibrotic changes, depending on the context [28]. In this regard, our observations showing that exposure to standard PDF promotes the formation of a comparable degree of peritoneal thickening without significant changes in the expression of the gene encoding type I collagen in both non-RF rats and RF rats, may be conceivable, although our current data do not allow us to precisely evaluate the individual roles of TGF-β1, Snail and MMP-2.…”

Section: Discussionmentioning

confidence: 99%

Peritoneal Fibrosis Induced by Intraperitoneal Methylglyoxal Injection: The Role of Concurrent Renal Dysfunction

Ōnishi

Akimoto²,

Morishita³

et al. 2014

Am J Nephrol

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Background: Peritoneal fibrosis (PF) is a serious pathophysiology of peritoneal dialysis (PD). An ongoing focus of research is the potential fibrogenic nature of methylglyoxal (MGO) in conventional PD fluid (PDF). The aim of the current study was to explore the effects of the uremic milieu on the promotion of PF by MGO using rats with adenine-induced renal failure (RF). Methods: Adenine-treated Sprague-Dawley rats were randomly assigned to receive continuous peritoneal injections of PDF with or without MGO for three weeks or were left untreated for the same duration. Rats without RF were also assigned to three groups. The peritoneal histology and expression levels of type I collagen, transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (αSMA), Snail, matrix metalloproteinase-2 (MMP-2), advanced glycation end-products (AGEs) and the receptor for AGE (RAGE) were then analyzed. Results: Peritoneal treatment with 5 mM MGO accelerated the fibrous peritoneal thickening progression promoted by exposure to standard PDF in the rats with RF, but not in the rats with a normal renal function. Treatment with MGO significantly augmented the proliferation of mesenchymal-like mesothelial cells, accumulation of AGE, de novo expression of αSMA and RAGE and gene expression of type I collagen, TGF-β1, Snail and MMP-2, whereas both MGO and RF alone had, at most, marginal effects on the changes in these biological parameters. Conclusions: In the present study, the adverse effects of MGO on the peritoneum became more prominent under conditions of a uremic milieu. These findings imply that MGO and uremia act cooperatively to induce PF.

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Epithelial-to-mesenchymal transition in fibrosis: Collagen type I expression is highly upregulated after EMT, but does not contribute to collagen deposition

Cited by 60 publications

References 36 publications

Proteomic Analysis of Minimally Damaged Renal Tubular Tissue from Two-Kidney-One-Clip Hypertensive Rats Demonstrates Extensive Changes Compared to Tissue from Controls

Proteomic Analysis of Minimally Damaged Renal Tubular Tissue from Two-Kidney-One-Clip Hypertensive Rats Demonstrates Extensive Changes Compared to Tissue from Controls

iRhom2 promotes lupus nephritis through TNF-α and EGFR signaling

Peritoneal Fibrosis Induced by Intraperitoneal Methylglyoxal Injection: The Role of Concurrent Renal Dysfunction

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