TY - JOUR
T1 - The role of epithelial-to-mesenchymal transition in renal fibrosis
AU - Zeisberg, Michael
AU - Kalluri, Raghu
N1 - Funding Information:
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.).
PY - 2004/3
Y1 - 2004/3
N2 - 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.
AB - 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.
KW - Bone morphogenic protein 7
KW - Epithelial-to-mesenchymal transition
KW - Renal fibrosis
KW - Transforming growth factor β
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U2 - 10.1007/s00109-003-0517-9
DO - 10.1007/s00109-003-0517-9
M3 - Review article
C2 - 14752606
AN - SCOPUS:1642379154
SN - 0946-2716
VL - 82
SP - 175
EP - 181
JO - Journal of Molecular Medicine
JF - Journal of Molecular Medicine
IS - 3
ER -