A critical look at growth factors and epithelial-to-mesenchymal transition in the adult kidney. Interrelationships between growth factors that regulate EMT in the adult kidney.
In the adult kidney, the cellular phenotypes are maintained by a strict balance of growth factors. Epithelial-to-mesenchymal transition (EMT) is a program whereby injured epithelial cells that function as ion and fluid transporters become matrix remodelling mesenchymal cells. This process requires either transcriptional repression of genes that maintain the epithelial phenotype and transcriptional activation, or relieved repression of genes needed for functional myofibroblasts. The transcriptional regulators are controlled by several integrated signalling pathways which are triggered by growth factors. Emerging evidence indicates that the growth factors TGFbeta/CTGF and BMP-7/HGF are the main determinants that maintain the two cellular phenotypes. Both TGFbeta and BMP-7 counteract the activity of each other by cross-inducing their respective inhibitory Smads. Both growth factors may also induce the expression of other factors that can change the cellular environment and enhance their function. Chronic kidney diseases (regardless of the aetiology of the disease) are associated with increased TGFbeta and CTGF expression levels which, in turn, have an inverse effect on the activity level of BMP-7 and HGF, leading to an EMT of injured tubular epithelial cells and a progression of the disease. A detailed understanding of the complex interrelationship between these growth factors may lead to the development of novel drugs.
Wahab
Nadia A
NA
Renal Section, Division of Medicine, Faculty of Medicine, Imperial College London, London, UK. nadia.wahab@imperial.ac.uk
Mason
Roger M
RM
D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D055513:Connective Tissue Growth Factor; D004847:Epithelial Cells / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000502:physiology; D017874:Immediate-Early Proteins / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D008648:Mesoderm / Q000502:physiology*; D051905:Smad6 Protein / Q000502:physiology; D051906:Smad7 Protein / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000502:physiology
D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D051905:Smad6 Protein; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; D017228:Hepatocyte Growth Factor