Journal ArticleDOI
BMP-7 counteracts TGF-β1–induced epithelial-to-mesenchymal transition and reverses chronic renal injury
Michael Zeisberg,Jun-ichi Hanai,Hikaru Sugimoto,Tadanori Mammoto,David M. Charytan,Frank Strutz,Raghu Kalluri +6 more
TLDR
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.Abstract:
Bone morphogenic protein (BMP)-7 is a 35-kDa homodimeric protein and a member of the transforming growth factor (TGF)-beta superfamily. BMP-7 expression is highest in the kidney, and its genetic deletion in mice leads to severe impairment of eye, skeletal and kidney development. Here we report that BMP-7 reverses TGF-beta1-induced epithelial-to-mesenchymal transition (EMT) by reinduction of E-cadherin, a key epithelial cell adhesion molecule. Additionally, we provide molecular evidence for Smad-dependent reversal of TGF-beta1-induced EMT by BMP-7 in renal tubular epithelial cells and mammary ductal epithelial cells. In the kidney, EMT-induced accumulation of myofibroblasts and subsequent tubular atrophy are considered key determinants of renal fibrosis during chronic renal injury. We therefore tested the potential of BMP-7 to reverse TGF-beta1-induced de novo EMT in a mouse model of chronic renal injury. Our results show that systemic administration of recombinant human BMP-7 leads to repair of severely damaged renal tubular epithelial cells, in association with reversal of chronic renal injury. Collectively, these results provide evidence of cross talk between BMP-7 and TGF-beta1 in the regulation of EMT in health and disease.read more
Citations
More filters
Journal ArticleDOI
The basics of epithelial-mesenchymal transition
Raghu Kalluri,Robert A. Weinberg +1 more
TL;DR: Processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias and the identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes.
Journal ArticleDOI
Microenvironmental regulation of tumor progression and metastasis.
TL;DR: The paradoxical roles of the tumor microenvironment during specific stages of cancer progression and metastasis are discussed, as well as recent therapeutic attempts to re-educate stromal cells within the TME to have anti-tumorigenic effects.
Journal ArticleDOI
Fibroblasts in cancer
TL;DR: Fibroblasts are a key determinant in the malignant progression of cancer and represent an important target for cancer therapies.
Journal ArticleDOI
Mechanisms of fibrosis: therapeutic translation for fibrotic disease
TL;DR: How cell-intrinsic changes in important structural cells can perpetuate the fibrotic response by regulating the differentiation, recruitment, proliferation and activation of extracellular matrix–producing myofibroblasts is described.
Journal ArticleDOI
Epithelial-mesenchymal transition and its implications for fibrosis.
Raghu Kalluri,Eric G. Neilson +1 more
TL;DR: 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.
References
More filters
Journal ArticleDOI
Epithelial–mesenchymal transitions in tumour progression
TL;DR: Epithelial–mesenchymal transition provides a new basis for understanding the progression of carcinoma towards dedifferentiated and more malignant states.
Journal ArticleDOI
TGF-beta signalling from cell membrane to nucleus through SMAD proteins
TL;DR: Inhibitory SMADs have been identified that block the activation of these pathway-restricted SMADS that direct transcription to effect the cell's response to TGF-β.
Journal ArticleDOI
The transcription factor Snail controls epithelial–mesenchymal transitions by repressing E-cadherin expression
Amparo Cano,Mirna Perez-Moreno,Isabel Rodrigo,Annamaria Locascio,Maria Blanco,Marta G. del Barrio,Francisco Portillo,M. Angela Nieto +7 more
TL;DR: It is shown that mouse Snail is a strong repressor of transcription of the E-cadherin gene, opening up new avenues for the design of specific anti-invasive drugs.
Journal ArticleDOI
Evidence that fibroblasts derive from epithelium during tissue fibrosis
Masayuki Iwano,David Plieth,Theodore M. Danoff,Theodore M. Danoff,Chengsen Xue,Hirokazu Okada,Hirokazu Okada,Eric G. Neilson +7 more
TL;DR: The findings suggest that a substantial number of organ fibroblasts appear through a novel reversal in the direction of epithelial cell fate, which highlights the potential plasticity of differentiated cells in adult tissues under pathologic conditions.
Journal ArticleDOI
How cells read TGF-beta signals.
TL;DR: The TGF-β family of cytokines can trigger a bewildering diversity of responses, depending on the genetic makeup and environment of the target cell.
Related Papers (5)
Epithelial-mesenchymal transition and its implications for fibrosis.
Raghu Kalluri,Eric G. Neilson +1 more