title: Brain natriuretic peptide modulates calcium homeostasis and epidermal growth factor receptor gene signalling in asthmatic airways smooth muscle cells.
abstract: The airway epithelium acts as a barrier and provides a critical interface between the body and the external environment. Brain natriuretic peptide (BNP) plays an important role in several bronchial functions, including relaxation. BNP relaxes airways by binding and activating natriuretic peptide receptor-A expressed from the airway epithelium. Although relaxation effect has been extensively investigated, less is known about BNP-regulated intracellular biomolecular pathways leading to bronchial relaxation. To this aim, we investigated BNP effects on gene signalling of airway smooth muscle cells (ASM) obtained from donors with asthma by using a RT(2) profiler™ PCR array. When compared with control, treatment for 2 h with supernatant from BNP-treated (1 μM) bronchial epithelial cells (BEAS-2B) induced in asthmatic ASM cells a rapid reduction of transcription of EGFR and genes involving in actin and calcium homeostasis, as those of Protein kinase C (PKC) and RhoA-ROCK gene pathways. Immunofluorescence and western blotting did not shown any difference comparing control and ASM cells treated with conditioned medium from BNP-treated BEAS-2B. This study provides evidence that the effect of BNP on relaxing bronchial in ASM cells is mediated from epithelium and associates to rapid changes of EGFR and calcium homeostasis-associated gene levels.
authors.affiliation: Department of Biomedicine and Prevention, Institute of Anatomic Pathology, University of Rome Tor Vergata, Rome, Italy; Tor Vergata University Policlinic of Rome, Italy.
authors.forename: Augusto
authors.initials: A
authors.lastname: Orlandi
authors.affiliation: Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Luigino
authors.initials: L
authors.lastname: Calzetta
authors.affiliation: Department of Biomedicine and Prevention, Institute of Anatomic Pathology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Doldo
authors.affiliation: Department of Biomedicine and Prevention, Institute of Anatomic Pathology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Tarquini
authors.affiliation: Department of Experimental Medicine, Second University of Naples, Naples, Italy.
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Matera
authors.affiliation: Department of Biomedicine and Prevention, Institute of Anatomic Pathology, University of Rome Tor Vergata, Rome, Italy. Electronic address: daniela.passeri@uniroma2.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Passeri
mesh_terms: D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D018773:Genes, erbB-1 / Q000187:drug effects*; D006706:Homeostasis; D006801:Humans; D009126:Muscle Relaxation / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D020097:Natriuretic Peptide, Brain; C066737:RHOA protein, human; D054460:rho-Associated Kinases; D011493:Protein Kinase C; D020742:rhoA GTP-Binding Protein; D002118:Calcium
keywords: Airway smooth muscle; BNP; Contraction; EGFR signalling; α-Smooth muscle actin