title: Chronic β-adrenergic stimulation increases ErbB receptors and cell proliferation in mouse kidney.
abstract: Although the sympathetic nervous system is involved in injury caused to the kidney by several stressors such as hypertension or ischemia/reperfusion, little is known about the effect of chronic adrenergic stimulation in the kidneys. Upon injury, however, the kidney possesses a high capacity for tubular cell regeneration and functional recovery. The ErbB1 receptor and its ligands play an essential role in this process. We studied the effects of chronic isoproterenol (ISO) administration (β-adrenoceptor agonist) in the mouse kidney. ISO induced a moderate and reversible loss of kidney weight and protein content that was not associated with renal dysfunction. We observed an increase in tubular cell proliferation (bromodeoxyuridine labeling) in ISO-treated mice in both the outer and inner cortex. ErbB1 (epidermal growth factor receptor) along with ErbB2 and ErbB3 (neuregulin receptor) were transiently overexpressed in ISO-treated mice, with an increase in protein but not mRNA content. All receptors were localized in the same nephron segments and cell types. Immunoprecipitation studies after epidermal growth factor or neuregulin-1β stimulation showed dynamic interaction of all four ErbB receptors. Therefore, we conclude that ErbB receptors may cooperate in the response to chronic β-adrenergic stimulation.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Catalonia, Spain.
authors.forename: Genís
authors.initials: G
authors.lastname: Campreciós
authors.forename: Elena
authors.initials: E
authors.lastname: Sánchez-Vizcaíno
authors.forename: Maria
authors.initials: M
authors.lastname: Soley
authors.forename: Ignasi
authors.initials: I
authors.lastname: Ramírez
mesh_terms: D018663:Adrenergic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology*; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D007677:Kidney Function Tests; D008297:Male; D051379:Mice; D020880:Neuregulins / Q000378:metabolism; D009929:Organ Size; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism; D012038:Regeneration; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D018663:Adrenergic Agents; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D007545:Isoproterenol; D020880:Neuregulins; D010656:Phenylephrine; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3