Bone morphogenetic protein 4, inhibitor of differentiation 1, and epidermal growth factor receptor regulate the survival of cochlear sensory epithelial cells

2013 ◽  
Vol 91 (4) ◽  
pp. 515-526 ◽  
Author(s):  
Junming Chen ◽  
Wei Sun ◽  
Yiqing Zheng ◽  
Hao Xiong ◽  
Yuexing Cai
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Epithelial Cells ◽  
Bone Morphogenetic Protein ◽  
Growth Factor Receptor ◽  
Bone Morphogenetic Protein 4 ◽  
Morphogenetic Protein ◽  
Epidermal Growth ◽  
Inhibitor Of Differentiation 1

scholarly journals Congenital Semilunar Valvulogenesis Defect in Mice Deficient in Phospholipase Cε

2005 ◽  
Vol 25 (6) ◽  
pp. 2191-2199 ◽  
Author(s):  
Makoto Tadano ◽  
Hironori Edamatsu ◽  
Susumu Minamisawa ◽  
Utako Yokoyama ◽  
Yoshihiro Ishikawa ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Bone Morphogenetic Protein ◽  
Growth Factor Receptor ◽  
Small Gtpases ◽  
Heparin Binding ◽  
Morphogenetic Protein ◽  
Epidermal Growth ◽  
Phospholipase Cε

ABSTRACT Phospholipase Cε is a novel class of phosphoinositide-specific phospholipase C, identified as a downstream effector of Ras and Rap small GTPases. We report here the first genetic analysis of its physiological function with mice whose phospholipase Cε is catalytically inactivated by gene targeting. The hearts of mice homozygous for the targeted allele develop congenital malformations of both the aortic and pulmonary valves, which cause a moderate to severe degree of regurgitation with mild stenosis and result in ventricular dilation. The malformation involves marked thickening of the valve leaflets, which seems to be caused by a defect in valve remodeling at the late stages of semilunar valvulogenesis. This phenotype has a remarkable resemblance to that of mice carrying an attenuated epidermal growth factor receptor or deficient in heparin-binding epidermal growth factor-like growth factor. Smad1/5/8, which is implicated in proliferation of the valve cells downstream of bone morphogenetic protein, shows aberrant activation at the margin of the developing semilunar valve tissues in embryos deficient in phospholipase Cε. These results suggest a crucial role of phospholipase Cε downstream of the epidermal growth factor receptor in controlling semilunar valvulogenesis through inhibition of bone morphogenetic protein signaling.

scholarly journals Involvement of Epidermal Growth Factor Receptor-Linked Signaling Responses in Pseudomonas fluorescens-Infected Alveolar Epithelial Cells

2011 ◽  
Vol 79 (5) ◽  
pp. 1998-2005 ◽  
Author(s):  
Hye Jin Choi ◽  
Chan Hee Seo ◽  
Seong Hwan Park ◽  
Hyun Yang ◽  
Kee Hun Do ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Epithelial Cells ◽  
Pseudomonas Fluorescens ◽  
Growth Factor Receptor ◽  
Airway Epithelial ◽  
Content Type ◽  
Proinflammatory Responses ◽  
Epidermal Growth

ABSTRACTPseudomonas fluorescensis an opportunistic indoor pathogen that can cause severe airway proinflammatory responses. Pulmonary epithelium, like other mucosal epithelial linings of the body, constitutes the first line of defense against airway microbial pathogens. Mucosal epithelial cells can be a sentinel of pathogenic bacteria via stimulation of specific cell surface receptors, including the epidermal growth factor receptor (EGFR) and Toll-like receptor (TLR). This study addressed the involvement of EGFR in airway epithelial pathogenesis byP. fluorescens. Human A549 pneumocytes showed prolonged production of proinflammatory interleukin-8 (IL-8) in response to infection withP. fluorescens, which was via the nuclear factor-kappa B (NF-κB) signaling pathway. Production of proinflammatory cytokine IL-8 was not mediated byP. fluorescenslipopolysaccharide, a representative TLR4 agonist, but was mediated through EGFR-linked signals activated by the opportunistic bacteria. Moreover, EGFR signals were involved in NF-κB signal-mediated production of proinflammatory cytokines. Along with persistent NF-κB activation,P. fluorescensenhanced the EGFR phosphorylation and subsequent activation of downstream mediators, including protein kinase B or extracellular-signal-regulated kinases 1/2. Blocking of EGFR-linked signals increased epithelial susceptibility to pathogen-induced epithelial cell death, suggesting protective roles of EGFR signals. Thus, airway epithelial exposure toP. fluorescenscan trigger antiapoptotic responses via EGFR and proinflammatory responses via TLR4-independent NF-κB signaling pathway in human pneumocytes.

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