The role of epithelial-to-mesenchymal transition in renal fibrosis
- 30 January 2004
- journal article
- review article
- Published by Springer Science and Business Media LLC in Journal of Molecular Medicine
- Vol. 82 (3), 175-181
- https://doi.org/10.1007/s00109-003-0517-9
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
This publication has 81 references indexed in Scilit:
- Elucidation of Smad Requirement in Transforming Growth Factor-β Type I Receptor-induced ResponsesPublished by Elsevier BV ,2003
- Signal Transduction by the TGF-β SuperfamilyScience, 2002
- Leaving the neighborhood: molecular mechanisms involved during epithelial‐mesenchymal transitionBioEssays, 2001
- The transcription factor Snail is a repressor of E-cadherin gene expression in epithelial tumour cellsNature, 2000
- E-Cadherin Transforms Embryonic Corneal Fibroblasts to Stratified Epithelium with DesmosomesCells Tissues Organs, 1996
- BMP-7 is an inducer of nephrogenesis, and is also required for eye development and skeletal patterning.Genes & Development, 1995
- A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye.Genes & Development, 1995
- Localization of Osteogenic Protein-1 (Bone Morphogenetic Protein-7) during Human Embryonic Development: High Affinity Binding to Basement MembranesBiochemical and Biophysical Research Communications, 1994
- Activation of an inducible c-FosER fusion protein causes loss of epithelial polarity and triggers epithelial-fibroblastoid cell conversionCell, 1992
- Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor roleCell, 1991