Epithelial-mesenchymal transition of tubular epithelial cells in human renal biopsies

Rastaldi, Maria Pia; Ferrario, Franco; Giardino, Laura; Dell’Antonio, Giacomo; Grillo, C; Grillo, Paolo; Strutz, Frank; Müller, Gerhard A.; Colasanti, G.; D’Amico, Giuseppe

doi:10.1046/j.1523-1755.2002.00430.x

Cited by 372 publications

(341 citation statements)

References 47 publications

Supporting

Mentioning

304

Contrasting

Unclassified

Order By: Relevance

“…In fact, proof of concept has only recently been reported in an elegant study using genetic engineering in mice (Iwano et al, 2002). In biopsies of diseased human kidney, single epithelial cells in tubular structures may show molecular evidence for EMT by coexpression of epithelial and mesenchymal markers (Rastaldi et al, 2002;Vongwiwatana et al, 2005). Although EMT has been widely adopted as an important mechanism that underlies epithelial degeneration and tissue fibrosis, the extent to which transitioning fibroblastoid cells contribute to accumulation of fibroblasts and ECM remains still unclear.…”

Section: Physiological Context Defines Distinct Roles and Features Ofmentioning

confidence: 99%

TGF-β and epithelial-to-mesenchymal transitions

2005

View full text Add to dashboard Cite

Remarkable phenotype plasticity of epithelial cells underlies morphogenesis, epithelial repair and tumor invasiveness. Detailed understanding of the contextual cues and molecular mediators that control epithelial plasticity will be required in order to develop viable therapeutic approaches targeting epithelial-to-mesenchymal transition (EMT), an advanced manifestation of epithelial plasticity. Members of the transforming growth factor (TGF-b) family of growth factors can initiate and maintain EMT in a variety of biological systems and pathophysiological context by activating major signaling pathways and transcriptional regulators integrated in extensive signaling networks. Here we will review the distinct physiological contexts of EMT and the underlying molecular signaling networks controlled by TGF-b.

show abstract

Section: Physiological Context Defines Distinct Roles and Features Ofmentioning

confidence: 99%

TGF-β and epithelial-to-mesenchymal transitions

2005

View full text Add to dashboard Cite

show abstract

“…In DN, EMT occurs as cells attempt to evade apoptosis as a consequence of exposure to pathophysiological stimuli [11][12]. Cells undergo transition in a process that involves the generation of active myofibroblasts, excessive deposition of ECM and destruction of normal tissue architecture [13][14]. The ability to switch phenotype stems from a unique plasticity of epithelial cells that has, up until recently, been universally accepted as the sole driving force behind the generation of interstital fibroblasts in kidney disease.…”

Section: Introductionmentioning

confidence: 99%

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

Hills

Squires

2011

Cytokine & Growth Factor Reviews

173

187

View full text Add to dashboard Cite

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.

show abstract

“…Although there are various apparent causes of renal fibrosis, this pathological feature may induce irreversible dysfunction of the kidney and eventually leads to end-stage kidney disease. Despite the debate whether injured epithelial cells can be the direct precursor of myofibroblasts via processing type II epithelial-to-mesenchymal transition (EMT), renal tubular epithelial cell is known as a primary cell in which pro-fibrotic cellular changes occur, contributing to the early development and progression of renal interstitial fibrosis [3][4][5][6][7][8][9] . These changes include decrease in tubular diameter, increase in expression of α-smooth muscle actin (α-SMA) and deposition of extracellular matrix, ultimately leading to tubular atrophy, loss of functional renal parenchyma, which contribute to renal interstitial fibrosis.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of STAT3 acetylation is associated with attenuated renal fibrosis in the obstructed kidney

Shen

Wang

et al. 2014

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim: To explore the relationship between the signal transducer and activator of transcription 3 (STAT3) signaling and renal fibrosis. Methods: Rat renal tubular epithelial NRK-52E cells were treated with angiotensin II (Ang II), nicotinamide (an inhibitor of NAD + -dependent class III protein deacetylases, SIRT1-7), or resveratrol (an activator of SIRT1). Mice underwent unilateral ureteral obstruction (UUO) were used for in vivo studies. Renal interstitial fibrosis was observed with HE and Masson's trichrome staining. STAT3 acetylation and phosphorylation, fibronectin, collagen I, collagen IV, and α-smooth muscle actin (α-SMA) levels were examined using Western blotting. Results: Nicotinamide (0.625-10 mmol/L) dose-dependently increased STAT3 acetylation on Lys685 and phosphorylation on Tyr705 in NRK-52E cells, accompanied by accumulation of fibronectin and collagen IV. Ang II increased STAT3 phosphorylation on Tyr705 and the expression of fibronectin, collagen IV and α-SMA in the cells. Pretreatment with resveratrol (12.5 μmol/L) blocked Ang II-induced effects in the cells. UUO induced marked STAT3 phosphorylation, fibronectin, collagen IV and α-SMA accumulation, and renal interstitial fibrosis in the obstructed kidneys, which were significantly attenuated by daily administration of resveratrol (100 mg/kg). Conclusion: STAT3 acetylation plays an important role in activation of STAT3 signaling pathway and consequent renal fibrosis.

show abstract

Epithelial-mesenchymal transition of tubular epithelial cells in human renal biopsies

Cited by 372 publications

References 47 publications

TGF-β and epithelial-to-mesenchymal transitions

TGF-β and epithelial-to-mesenchymal transitions

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

Inhibition of STAT3 acetylation is associated with attenuated renal fibrosis in the obstructed kidney

Contact Info

Product

Resources

About