title: Deletion of ErbB4 accelerates polycystic kidney disease progression in cpk mice.
abstract: ErbB4 is highly expressed in the cystic kidneys with polycystic kidney diseases. To investigate its potential role in cystogenesis, cpk mice carrying a heart-rescued ErbB4 deletion were generated. Accelerated cyst progression and renal function deterioration were noted as early as 10 days postnatally in cpk mice with ErbB4 deletion compared to cpk mice, as indicated by increased cystic index, higher kidney weight to body weight ratios, and elevated BUN levels. No apparent defects in renal development were noted with ErbB4 deletion itself. Increased cell proliferation was predominately seen in the cortex of cystic kidneys with or without ErbB4 deletion. However, there was significantly more cell proliferation in the cyst-lining epithelial cells in cpk mice with ErbB4 deletion. TUNEL staining localized apoptotic cells mainly to the renal medulla. There were significantly more apoptotic cells in the cyst-lining epithelial cells in ErbB4-deleted cpk kidneys, with decreased levels of cyclin D1, increased levels of p21, p27, and cleaved caspase 3. Thus, lack of ErbB4 may contribute to elevated cell proliferation and unbalanced cell apoptosis, resulting in accelerated cyst formation and early renal function deterioration. These studies suggest that the high level of ErbB4 expression seen in cpk mice may exert relative cytoprotective effects in renal epithelia.
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Zeng
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Miyazawa
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Lance A
authors.initials: LA
authors.lastname: Kloepfer
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Harris
mesh_terms: D000818:Animals; D017209:Apoptosis; D001806:Blood Urea Nitrogen; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D056741:Cyclin D / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism*; D005355:Fibrosis; D017353:Gene Deletion; D007672:Kidney Cortex / Q000473:pathology*; D007679:Kidney Medulla / Q000473:pathology*; D051379:Mice; D009929:Organ Size; D007690:Polycystic Kidney Diseases / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D066247:Receptor, ErbB-4 / Q000235:genetics* / Q000378:metabolism
chemical_list: D056741:Cyclin D; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4; D053148:Caspase 3