Tubular epithelial-myofibroblast transdifferentiation in progressive tubulointerstitial fibrosis in 5/6 nephrectomized rats

Ng, Yee‐Yung; Huang, Tung-Po; Yang, Wancai; Chen, Zhengping; Yang, An-Hang; Mu, Wei; Nikolic-Paterson, David J.; Atkins, Robert C.; Lan, Hui‐Yao

doi:10.1046/j.1523-1755.1998.00076.x

Cited by 364 publications

(265 citation statements)

References 29 publications

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“…35 Although these myofibroblasts are generally presumed to derive from local activation of residential fibroblasts under diseased conditions, evidence suggests that these cells may also derive from tubular epithelial cells via a process known as epithelial to mesenchymal transition. 36,37 Consistent with this view, our preliminary results show that TGF-␤1 can induce ␣SMA expression in both cultured renal interstitial fibroblasts and tubular epithelial cells in vitro (unpublished data). Regardless of the mechanisms, the fact that exogenous HGF inhibits myofibroblast activation in the obstructed kidneys underscores that exogenous HGF precisely targets a key event, the activation of principal matrix-producing cells, during renal fibrogenesis.…”

Section: Figure 7 Exogenous Hgf Inhibits Tgf-␤1 and Tgf-␤ Type I Recesupporting

confidence: 73%

Systemic administration of naked plasmid encoding hepatocyte growth factor ameliorates chronic renal fibrosis in mice

2001

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Section: Figure 7 Exogenous Hgf Inhibits Tgf-␤1 and Tgf-␤ Type I Recesupporting

confidence: 73%

Systemic administration of naked plasmid encoding hepatocyte growth factor ameliorates chronic renal fibrosis in mice

2001

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“…However, transitions do occur particularly during oncogenesis [31] and fibrogenesis [32,33]. This process has been particularly studied in renal fibrosis.…”

Section: Discussionmentioning

confidence: 99%

“…This process has been particularly studied in renal fibrosis. It has been hypothesized that when basement membrane is injured by matrix metaroproteinase, epithelial cells that detach from their basement membrane may enter into epithelial-mesenchymal transition, express HSP47 and other mesenchymal markers and divide as fibroblasts [33][34][35]. Whether this process takes place in the lung in IPF or in other forms of pulmonary fibrosis is largely unknown, but urgent evaluation in vitro and in vivo would be necessary.…”

Section: Discussionmentioning

confidence: 99%

Localization of HSP47 mRNA in murine bleomycin-induced pulmonary fibrosis

et al. 2010

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Heat shock protein (HSP) 47 is a collagen-specific molecular chaperone that has been shown to play a major role in the processing and/or secretion of procollagen. However, the knowledge on which cells are actually synthesizing HSP47 in the lung parenchyma in pulmonary fibrosis was only limited. The aim of the present study was to investigate the localization of HSP47 messenger ribonucleic acid (mRNA) in normal lung, and in the lungs of mice in bleomycin-induced pulmonary fibrosis, using in situ hybridization.For the purpose, ICR mice were intravenously injected with 10 mg/kg/day of bleomycin for 5 consecutive days. The lung cells expressing HSP47 mRNA were identified in control (saline alone) and bleomycin-treated mice by in situ hybridization. The signal for HSP47 mRNA was markedly increased in bleomycin-treated lungs compared with that of controls. HSP47 mRNA was localized in -smooth muscle actin-positive myofibroblasts, surfactant protein A-positive type II pneumocytes and F4/80 positive macrophages in the active fibrotic areas. These results suggest that these cells may synthesize procollagen in the fibrotic process of bleomycin-treated lungs through upregulation of HSP47 mRNA and play an important role in fibrogenesis.

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“…The authors demonstrated that of those matrix producing cells resident within the tubulointerstitial space, 36% were of epithelial origin and thus derived from renal tubular epithelium through EMT [10]. The underlying pathology of EMT has since been observed in renal biopsies from diseased kidney where the proportion of cells undergoing transition correlated to both the level of serum creatinine and the degree of interstitial fibrosis [88]. Evidence for EMT in vivo has since been described in various forms of of CKD, including diabetic nephropathy [89] [90].…”

Section: Tgf-β1 Emt and Fibrosis In Diabetic Nephropathymentioning

confidence: 99%

The role of TGF-β and epithelial-to mesenchymal transition in diabetic nephropathy

Hills

Squires

2011

Cytokine & Growth Factor Reviews

162

185

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Transforming Growth Factor-beta (TGF-β) is a pro-sclerotic cytokine widely associated with the development of fibrosis in diabetic nephropathy. Central to the underlying pathology of tubulointerstitial fibrosis is epithelial-to-mesenchymal transition (EMT), or the trans-differentiation of tubular epithelial cells into myofibroblasts. This process is accompanied by a number of key morphological and phenotypic changes culminating in detachment of cells from the tubular basement membrane and migration into the interstitium. Ultimately these cells reside as activated myofibroblasts and further exacerbate the state of fibrosis. A large body of evidence supports a role for TGF-β and downstream Smad signaling in the development and progression of renal fibrosis. Here we discuss a role for TGF-β as the principle effector in the development of renal fibrosis in diabetic nephropathy, focusing on the role of the TGF-β1 isoform and its downstream signaling intermediates, the Smad proteins. Specifically we review evidence for TGF-β1 induced EMT in both the proximal and distal regions of the nephron and describe potential therapeutic strategies that may target TGF-β1 activity.

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Tubular epithelial-myofibroblast transdifferentiation in progressive tubulointerstitial fibrosis in 5/6 nephrectomized rats

Cited by 364 publications

References 29 publications

Systemic administration of naked plasmid encoding hepatocyte growth factor ameliorates chronic renal fibrosis in mice

Systemic administration of naked plasmid encoding hepatocyte growth factor ameliorates chronic renal fibrosis in mice

Localization of HSP47 mRNA in murine bleomycin-induced pulmonary fibrosis

The role of TGF-β and epithelial-to mesenchymal transition in diabetic nephropathy

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