Abstract
Polycystic kidney diseases (PKDs) represent a group of progressive genetic renal disorders that are characterized by the development of renal cysts that lead to end-stage renal disease. The rapid advance in our understanding of the pathogenesis of PKDs is revealing possible targets to slow down the progression of PKD. Among them, the epidermal growth factor receptor (EGFR) family members (ErbBs) as well as their ligands, such as EGF, HB-EGF, TGF-α, have emerged as important mediators of cystic formation and growth in PKD. ErbB receptors are either overexpressed or mislocated to the apical surface of cystic tubular epithelium in PKD instead of the basolateral localization seen in the normal adult kidney. Preclinical studies have demonstrated that inhibition of ErbB tyrosine kinase activity and/or reduced ErbB ligand availability significantly reduced cystogenesis in several murine PKD models (pcy, jck and cpk) and in the Han: SPRD rat ADPKD model. In this review, we will discuss the expression patterns, possible roles and related signaling molecules of the ErbB axis in PKD and the pharmaceutical potentials for future therapeutic development.
Keywords: PKD, ErbBs, expression, function, signaling pathways, therapies
Current Signal Transduction Therapy
Title: The ErbB Receptors and Their Ligands in PKD, an Overview
Volume: 5 Issue: 2
Author(s): Fenghua Zeng and Raymond C. Harris
Affiliation:
Keywords: PKD, ErbBs, expression, function, signaling pathways, therapies
Abstract: Polycystic kidney diseases (PKDs) represent a group of progressive genetic renal disorders that are characterized by the development of renal cysts that lead to end-stage renal disease. The rapid advance in our understanding of the pathogenesis of PKDs is revealing possible targets to slow down the progression of PKD. Among them, the epidermal growth factor receptor (EGFR) family members (ErbBs) as well as their ligands, such as EGF, HB-EGF, TGF-α, have emerged as important mediators of cystic formation and growth in PKD. ErbB receptors are either overexpressed or mislocated to the apical surface of cystic tubular epithelium in PKD instead of the basolateral localization seen in the normal adult kidney. Preclinical studies have demonstrated that inhibition of ErbB tyrosine kinase activity and/or reduced ErbB ligand availability significantly reduced cystogenesis in several murine PKD models (pcy, jck and cpk) and in the Han: SPRD rat ADPKD model. In this review, we will discuss the expression patterns, possible roles and related signaling molecules of the ErbB axis in PKD and the pharmaceutical potentials for future therapeutic development.
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Cite this article as:
Zeng Fenghua and C. Harris Raymond, The ErbB Receptors and Their Ligands in PKD, an Overview, Current Signal Transduction Therapy 2010; 5 (2) . https://dx.doi.org/10.2174/157436210791112145
DOI https://dx.doi.org/10.2174/157436210791112145 |
Print ISSN 1574-3624 |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-389X |
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