epidermal-growth-factor and Respiratory-Tract-Diseases

Cutis laxa (CL) is a rare connective tissue disorder characterized by wrinkled, abundant and sagging skin, sometimes associated with systemic impairment. Biallelic alterations in latent transforming growth factor beta-binding protein 4 gene (LTBP4) cause autosomal recessive type 1C cutis laxa (ARCL1C, MIM #613177). The present report describes the case of a 17-months-old girl with cutis laxa together with a literature review of previous ARCL1C cases. Based on proband main clinical signs (cutis laxa and pulmonary emphysema), clinical exome sequencing (CES) was performed and showed a new nine base-pairs homozygous in-frame deletion in LTBP4 gene. RT-PCR and cDNA Sanger sequencing were performed in order to clarify its impact on RNA. This report demonstrates that a genetic alteration in the EGF-like 14 domain calcium-binding motif of LTBP4 gene is likely responsible for cutis laxa in our patient.

Topics: Calcium; Cartilage Diseases; Cutis Laxa; DNA, Complementary; Epidermal Growth Factor; Female; Gastrointestinal Diseases; Humans; Infant; Latent TGF-beta Binding Proteins; Respiratory Tract Diseases; RNA; Transforming Growth Factor beta; Urologic Diseases

Respiratory diseases such as asthma and COPD (chronic obstructive pulmonary disease) are characterized by increased numbers of goblet cells and excessive mucus production, which contribute to the underlying disease pathology. Mucins form a major component of the mucus contributing to its viscoelastic properties, and in the airways the mucins MUC5AC and MUC5B are found at increased levels in both asthmatic and COPD subjects. A diverse range of stimuli have been shown to regulate MUC5AC expression and cause increases in the number of mucus-producing goblet cells. Perhaps the best characterized of these mediators is the cytokine IL (interleukin)-13, which causes increases in MUC5AC-expressing goblet cells in the airways. Several transcription factors have been linked with goblet cell formation and mucus production and include STAT6 (signal transducer and activator of transcription 6), FOXA2 (forkhead box A2) and the SPDEF [SAM (sterile alpha motif) domain-containing prostate-derived Ets factor]. In mouse airways, goblet cells are normally rare or absent, but increase rapidly in number in response to certain stimuli. The origins of these goblet cells are not well understood, although Clara cells and ciliated cells have been implicated as goblet cell progenitors. An understanding of the origin and processes regulating goblet cell formation in human airway epithelial cells has important implications for the identification of therapeutic targets to treat respiratory diseases.

Topics: Animals; Epidermal Growth Factor; Gene Expression Regulation; Goblet Cells; Hepatocyte Nuclear Factor 3-beta; Humans; Interleukin-13; Mucin 5AC; Mucins; Respiratory Tract Diseases; STAT6 Transcription Factor

Lysophosphatidic acid (LPA) is a bioactive lipid mediator and important component of serum. Studies over the past several years which have documented diverse effects of LPA on multiple types of airway cells and which suggest possible involvement of LPA in lung disease are reviewed here. LPA enhances contractility of airway smooth muscle. It also stimulates proliferation of cultured airway smooth muscle cells and exhibits a striking synergism with epidermal growth factor (EGF) for stimulating mitogenesis. Recent studies of the molecular components and signaling pathways mediating synergism are described, including LPA-induced upregulation of EGF receptors and activation of multiple transcription factors by both LPA and EGF. A model for the effects of LPA and EGF on mitogenesis that includes EGF receptor upregulation and synergism between Ras and Rho for activation of the transcription factor AP-1 is presented. LPA stimulates fibronectin secretion and filopodia extension in airway epithelial cells as well as proliferation and collagen gel contraction by lung fibroblasts. A hypothesis for LPA involvement in the airway repair and remodeling, which contribute to the pathology of asthma and other airway diseases, is presented, and future directions for research into the roles of LPA in airway function and disease are suggested.

Topics: Animals; Asthma; Cell Division; Epidermal Growth Factor; Humans; Lysophospholipids; MAP Kinase Signaling System; Respiratory Mucosa; Respiratory Physiological Phenomena; Respiratory Tract Diseases; Signal Transduction

Airway hypersecretion is a serious and presently untreatable symptom of chronic inflammatory airway diseases. Recently, it has been discovered that epithelial growth factor receptor expression and activation causes mucin production in airways. An epithelial growth factor receptor pathway is implicated in mucus cell differentiation induced by various stimuli; therefore, inhibition of the epithelial growth factor receptor transduction cascade may provide effective new treatments for hypersecretory airway diseases.

Topics: Allergens; Animals; Epidermal Growth Factor; ErbB Receptors; Humans; Mucins; Mucus; Respiratory Tract Diseases; Respiratory Tract Infections

The aim of this study was to evaluate the effect of carvacrol on serum level of inflammatory mediators and respiratory symptoms in the veterans exposed to sulfur mustard (SM).. Twenty-one patients who were exposed to SM more than two decades' ago were divided to placebo and carvacrol (1.2 mg/kg/day) treated groups. Serum levels of Tumor Necrosis Factor-α (TNF-α), Monocyte chemotactic protein-1 (MCP-1), Vascular endothelial growth factor (VEGF), Epidermal growth factor (EGF), forced expiratory volume-one second (FEV. FEV. Two months' treatment with carvacrol reduced inflammatory cytokine and chemokine while increased anti-inflammatory cytokines and improved respiratory symptom and FEV. This trial was registered under IRCT2014031617020N1 at http://www.irct.ir/.

Topics: Chemokine CCL2; Chemokines; Cough; Cymenes; Cytokines; Epidermal Growth Factor; Forced Expiratory Volume; Humans; Inflammation Mediators; Inhalation Exposure; Middle Aged; Mustard Gas; Placebos; Respiratory Function Tests; Respiratory Sounds; Respiratory Tract Diseases; Terpenes; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Veterans

Topics: Air Pollutants; Allergens; Animals; Epidermal Growth Factor; Epithelium; ErbB Receptors; Expectorants; Humans; Mucus; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases