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

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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.

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Fig. 1a–d
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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

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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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Correspondence to Raghu Kalluri.

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Zeisberg, M., Kalluri, R. The role of epithelial-to-mesenchymal transition in renal fibrosis. J Mol Med 82, 175–181 (2004). https://doi.org/10.1007/s00109-003-0517-9

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