Journal of Molecular Medicine

, Volume 82, Issue 3, pp 175–181 | Cite as

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

Review

Abstract

Epithelial-to-mesenchymal transition (EMT) involving injured epithelial cells plays an important role in the progression of fibrosis in the kidney. Tubular epithelial cells can acquire a mesenchymal phenotype, and enhanced migratory capacity enabling them to transit from the renal tubular microenvironment into the interstitial space and escape potential apoptotic cell death. EMT is a major contributor to the pathogenesis of renal fibrosis, as it leads to a substantial increase in the number of myofibroblasts, leading to tubular atrophy. However, recent findings suggest that EMT involving tubular epithelial cell is a reversible process, potentially determined by the surviving cells to facilitate the repopulation of injured tubules with new functional epithelia. Major regulators of renal epithelial cell plasticity in the kidney are two multifunctional growth factors, bone morphogenic protein-7 (BMP-7) and transforming growth factor β1 (TGF-β1). While TGF-β1 is a well-established inducer of EMT involving renal tubular epithelial cells, BMP-7 reverses EMT by directly counteracting TGF-β-induced Smad-dependent cell signaling in renal tubular epithelial cells. Such antagonism results in the repair of injured kidneys, suggesting that modulation of epithelial cell plasticity has therapeutic advantages.

Keywords

Epithelial-to-mesenchymal transition Renal fibrosis Bone morphogenic protein 7 Transforming growth factor β 

Abbreviations

ALK

Activin-like kinase

bFGF

Basic fibroblast growth factor

BMP

Bone morphogenic protein

ECM

Extracellular matrix

EGF

Epithelial growth factor

EMT

Epithelial-to-mesenchymal transition

FSP1

Fibroblast specific protein 1

IL-1

Interleukin 1

LAP

Latency-associated polypeptide

MET

Mesenchymal-to-epithelial transition

MMP

Matrix metalloproteinase

TBM

Tubular basement membrane

TGF

Transforming growth factor

Notes

Acknowledgements

The authors are supported by grants DK62987 and DK55001 from the NIH, research funds for the Center for Matrix Biology at the Beth Israel Deaconess Medical Center, the Espinosa Liver Fibrosis Fund, the Stop and Shop Pediatric Brain Tumor Foundation (to M.Z.) and a grant from the Deutsche Forschungsgemeinschaft DFG ZE5231/1 (to M.Z.).

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Center for Matrix Biology, Department of MedicineBeth Israel Deaconess Medical Center and Harvard Medical SchoolBostonUSA
  2. 2.Center for Matrix Biology, DANA 514 Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonUSA

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