TGF-β-induced EMT: mechanisms and implications for fibrotic lung disease

@article{Willis2007TGFinducedEM,
  title={TGF-$\beta$-induced EMT: mechanisms and implications for fibrotic lung disease},
  author={Brigham C. Willis and Zea Borok},
  journal={American Journal of Physiology-lung Cellular and Molecular Physiology},
  year={2007},
  volume={293}
}
  • B. WillisZ. Borok
  • Published 1 September 2007
  • Medicine, Biology
  • American Journal of Physiology-lung Cellular and Molecular Physiology
Epithelial-mesenchymal transition (EMT), a process whereby fully differentiated epithelial cells undergo transition to a mesenchymal phenotype giving rise to fibroblasts and myofibroblasts, is increasingly recognized as playing an important role in repair and scar formation following epithelial injury. The extent to which this process contributes to fibrosis following injury in the lung is a subject of active investigation. Recently, it was demonstrated that transforming growth factor (TGF… 

Figures from this paper

New insights into epithelial-mesenchymal transition in kidney fibrosis.

  • Youhua Liu
  • Medicine, Biology
    Journal of the American Society of Nephrology : JASN
  • 2010
This review highlights the current understanding of EMT and its underlying mechanisms to stimulate further discussion on its role, not only in the pathogenesis of renal interstitial fibrosis but also in the onset of podocyte dysfunction, proteinuria, and glomerulosclerosis.

Biomechanics of TGFβ-induced epithelial-mesenchymal transition: implications for fibrosis and cancer

The role that EMT plays in fibrogenesis and in the progression of cancer, with particular emphasis placed on biophysical signaling mechanisms that control the EMT program is described and specific TGFβ-induced intracellular signaling cascades that are affected by cell- and tissue-level mechanics are described.

An Assessment of Epithelial and Mesenchymal Phenotypes in Experimental and Clinical Pulmonary Fibrosis

Evidence of alterations in epithelial and mesenchymal markers in experimental models of lung fibrosis and how these findings are relevant to clinical disease is provided.

Involvement of epithelial-mesenchymal transition in methotrexate-induced pulmonary fibrosis.

The expression of EMT markers such as E-cadherin, α-SMA, and vimentin were investigated by immunofluorescence analysis in mouse lung tissues after administration of methotrexate, suggesting that MTX-induced pulmonary fibrosis occurs via EMT.

Epithelial-mesenchymal transition in primary human bronchial epithelial cells is Smad-dependent and enhanced by fibronectin and TNF-α

This study tests whether primary human bronchial epithelial cells are able to undergo EMT in vitro and to investigate the effect of various profibrotic factors in the process, and suggests that bone morphogenetic protein-4 is likely to have a context dependent effect during the EMT of HBECs, being able to induce the expression of EMT markers and to inhibit TGF-β induced epithelial transdifferentiation.

SNAI transcription factors mediate epithelial–mesenchymal transition in lung fibrosis

The results demonstrate that TGFβ1-induced EMT in ATII cells is essentially controlled by the expression and nuclear translocation of SNAI transcription factors, and suggests that SNAi-mediated EMT may contribute to the fibroblast pool in idiopathic pulmonary fibrosis.

Epithelial–Mesenchymal Transition in the Pathogenesis of Idiopathic Pulmonary Fibrosis

The overall available evidence conceptualizes EMT as an alternative cell and tissue normal regeneration, which could open the way to novel diagnostic and prognostic biomarkers, as well as to more effective treatment options.

Induction of epithelial-mesenchymal transition in primary airway epithelial cells from patients with asthma by transforming growth factor-beta1.

The hypothesis that epithelial repair in asthmatic airways is dysregulated is supported, as TGF-beta1 induces EMT in a Smad3-dependent manner in primary AECs.

Twist: A Regulator of Epithelial-Mesenchymal Transition in Lung Fibrosis

It is concluded that Twist contributes to EMT in the model of virus-induced pulmonary fibrosis, and speculated that in some IPF cases, γ-herpes virus infection with EBV might be a source of injury precipitating EMT through the expression of Twist.

β-catenin induces A549 alveolar epithelial cell mesenchymal transition during pulmonary fibrosis.

Alveolar epithelial cell injury and profibrogenic cytokine release in EMT and their association with the Wnt/β‑catenin signaling pathway in a mouse model of bleomycin‑induced pulmonary fibrosis demonstrated that activation of the Wnnt signaling pathway was capable of inducing an EMT program in the lung epithelial cells through β‑Catenin.
...

References

SHOWING 1-10 OF 153 REFERENCES

TGF-β1 induces human alveolar epithelial to mesenchymal cell transition (EMT)

The data showed that TGF-β1 induced A549 cells with an alveolar epithelial type II cell phenotype to undergo EMT in a time-and concentration-dependent manner, and cells that had undergone EMT showed enhanced expression of markers of fibrogenesis including collagens type I and III and CTGF.

The role of epithelial-to-mesenchymal transition in renal fibrosis

BMP-7 reverses EMT by directly counteracting TGF-β-induced Smad-dependent cell signaling in renal tubular epithelial cells, which results in the repair of injured kidneys, suggesting that modulation of epithelial cell plasticity has therapeutic advantages.

Epithelial to mesenchymal transition in renal fibrogenesis: pathologic significance, molecular mechanism, and therapeutic intervention.

  • Youhua Liu
  • Biology, Medicine
    Journal of the American Society of Nephrology : JASN
  • 2004
A comprehensive review of recent advances on understanding the pathologic significance, molecular mechanism, and therapeutic intervention of EMT in the setting of chronic renal fibrosis is provided.

Epithelial origin of myofibroblasts during fibrosis in the lung.

It is hoped that a major shift in current paradigms regarding the genesis of pulmonary fibrosis and dissection of the relevant pathways may allow development of targeted interventions that could potentially reverse the process and ameliorate the debilitating effects of abnormal repair and progressive fibrosis.

Epithelial-mesenchymal transition and its implications for fibrosis.

This review highlights recent advances in the process of EMT signaling in health and disease and how it may be attenuated or reversed by selective cytokines and growth factors.

Phenotype of airway epithelial cells suggests epithelial to mesenchymal cell transition in clinically stable lung transplant recipients

Evidence of EMT markers in lung allografts of patients without loss of lung function is provided, indicating that the EMT process may represent a final common pathway following injury in more common diseases characterised by airway remodelling.

BMP-7 counteracts TGF-β1–induced epithelial-to-mesenchymal transition and reverses chronic renal injury

It is reported that BMP-7 reverses TGF-β1–induced epithelial-to-mesenchymal transition (EMT) by reinduction of E-cadherin, a key epithelial cell adhesion molecule, which provides evidence of cross talk between B MP-7 and TGF -β1 in the regulation of EMT in health and disease.

Role for integrin-linked kinase in mediating tubular epithelial to mesenchymal transition and renal interstitial fibrogenesis.

It is demonstrated that integrin-linked kinase (ILK) plays an important role in mediating tubular EMT induced by TGF-beta1 and likely plays a crucial role in the pathogenesis of chronic renal fibrosis.

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

The results suggest that, via transition to a mesenchymal phenotype, TEC can produce ECM proteins in human disease and directly intervene in the fibrotic processes.

The epithelial–mesenchymal transition: new insights in signaling, development, and disease

Interest and research in EMT are currently at a high level, as seen by the attendance at the recent EMT meeting in Vancouver, Canada, and the identification of new markers to facilitate the observation of EMT in vivo.
...