Pulmonary Cell News Volume 6.31 | Aug 10 2017

TOP STORY

Senolytic Drugs Target Alveolar Epithelial Cell Function and Attenuate Experimental Lung Fibrosis Ex Vivo

Investigators demonstrated that lung epithelial cells exhibit increased P16 and P21 expression as well as senescence-associated β-galactosidase activity in experimental and human lung fibrosis tissue and primary cells. Pharmacological clearance of senescent cells by induction of apoptosis in fibrotic ATII cells or ex vivo three-dimensional lung tissue cultures reduced senescence-associated secretory phenotype factors and extracellular matrix markers, while increasing alveolar epithelial markers. [Eur Respir J] Full Article

(Ranked by impact factor of the journal)

Pseudomonas aeruginosa LasB Protease Impairs Innate Immunity in Mice and Humans by Targeting a Lung Epithelial Cystic Fibrosis Transmembrane Regulator–IL-6–Antimicrobial–Repair Pathway

Researchers evaluated the effect of P. aeruginosa elastase LasB, an important virulence factor secreted by the type II secretion system, on ion transport, innate immune responses and epithelial repair, both in vitro and in vivo. They showed that LasB was the most abundant protein in wild-type pseudomonas aeruginosa O1 secretomes and that it decreased epithelial CF transmembrane conductance regulator expression and activity. [Thorax] Full Article

MicroRNA-34/449 Targets IGFBP-3 and Attenuates Airway Remodeling by Suppressing Nur77-Mediated Autophagy

Investigators examined the role of epithelial miRNAs in autophagy-mediated airway remodeling and identified the factors involved and the underlying mechanisms. miR-34/449 were downregulated in patients with asthma in parallel with the upregulation of autophagy-related proteins. [Cell Death Dis] Full Article

Targeting the PI3K/Akt/mTOR Signaling Pathway in Cystic Fibrosis

Deletion of phenylalanine 508 of the CF transmembrane conductance regulator (ΔF508 CFTR) is a major cause of CF, one of the most common inherited childhood diseases. Using protein interaction profiling and global bioinformatics analysis, scientists revealed mammalian target of rapamycin (mTOR) signaling components to be associated with ΔF508 CFTR. Their results demonstrated upregulated mTOR activity in ΔF508 CF bronchial epithelial cells. [Sci Rep] Full Article

Safety and Efficacy of Allogeneic Lung Spheroid Cells in a Mismatched Rat Model of Pulmonary Fibrosis

The authors compared the efficacy and safety of syngeneic and allogeneic lung spheroid cells (LSCs) in immuno-competent rats with bleomycin-induced pulmonary inflammation in an effort to mitigate fibrosis development. They found that infusion of allogeneic LSCs reduces the progression of inflammation and fibrotic manifestation and preserves epithelial and endothelial health without eliciting significant immune rejection. [Stem Cells Transl Med] Full Article

Tannic Acid Attenuates TGF-β1-Induced Epithelial-to-Mesenchymal Transition by Effectively Intervening TGF-β Signaling in Lung Epithelial Cells

Both the human adenocarcinomic alveolar epithelial and normal bronchial epithelial cells were treated with transforming growth factor-β1 (TGF-β1) with or without tannic acid (TA). Results showed that TA addition markedly inhibited TGF-β1-induced epithelial-to-mesenchymal transition, as assessed by reduced expression of N-cadherin, type-1-collagen, fibronectin and vimentin. [J Cell Physiol] Abstract

LUNG CANCER

MiR-1254 Suppresses HO-1 Expression through Seed Region-Dependent Silencing and Non-Seed Interaction with TFAP2A Transcript to Attenuate NSCLC Growth

The authors demonstrated a miRNA-induced dual regulation of heme oxygenase-1 (HO-1), via seed region and non-seed region, consequently inhibited tumor growth of non-small cell lung carcinoma (NSCLC). They identified miR-1254 as a negative regulator inhibiting HO-1 translation by directly targeting HO-1 3’UTR via its seed region, and suppressing HO-1 transcription via non-seed region-dependent inhibition of transcriptional factor AP-2 alpha (TFAP2A), a transcriptional activator of HO-1. [PLoS Genet] Full Article

Pecanex Functions as a Competitive Endogenous RNA of S-Phase Kinase Associated Protein 2 in Lung Cancer

Scientists showed that pecanex (PCNX) positively regulates the mRNA and protein expressions of S-phase kinase associated protein 2 (Skp2) in miRNA- and 3′-UTR-dependent manners. miR-26, miR-182, miR-340 and miR-506 were verified as the common miRNAs shared by Skp2 and PCNX. [Cancer Lett] Abstract

Rho Inhibition by Lovastatin Affects Apoptosis and DSB Repair of Primary Human Lung Cells In Vitro and Lung Tissue In Vivo following Fractionated Irradiation

Researchers investigated whether pharmacological targeting of Rho signaling by the HMG-CoA-reductase inhibitor lovastatin influences ionizing radiation-induced toxicity in primary human lung fibroblasts, lung epithelial and lung microvascular endothelial cells in vitro and subchronic mouse lung tissue damage following hypo-fractionated irradiation. [Cell Death Dis] Full Article

SLC39A4 Expression Is Associated with Enhanced Cell Migration, Cisplatin Resistance, and Poor Survival in Non-Small Cell Lung Cancer

Integrated analysis of gene expression in non-small cell lung cancer revealed that SLC39A4 expression is significantly correlated with increased tumor size and regional lymph node spread, as well as shorter overall survival and disease-free survival. SLC39A4 silencing by lentivirus-mediated shRNA blocked human lung cancer cell epithelial-mesenchymal transition and metastasis in vitro and in vivo, respectively. [Sci Rep] Full Article

FBXO4 Inhibits Lung Cancer Cell Survival by Targeting Mcl-1 for Degradation

Scientists report that myeloid cell leukemia-1 (Mcl-1) protein levels inversely correlated with FBXO4 expression, but not other F-box proteins examined, in lung cancer cell lines and lung cancer patient samples. FBXO4 was the E3 ubiquitin ligase to interact with and promote Mcl-1 ubiquitination and degradation. [Cancer Gene Ther] Abstract

Acute Respiratory Distress Syndrome

The authors discuss the current understanding of the pathobiology and treatment of acute respiratory distress syndrome. [N Engl J Med] Abstract

Stem Cells in Pulmonary Disease and Regeneration

Scientists present the current understanding of the stem cell populations within the pulmonary epithelium, and describe ongoing efforts to use these stem cell populations to generate models for exploring lung function and disease. [Chest] Abstract

Visit our reviews page to see a complete list of reviews in the pulmonary cell research field.

FDA Allows WIN Consortium to Proceed with Targeted Tri-Therapy Clinical Trial in First Line Treatment of Metastatic Non Small Cell Lung Cancer

WIN Consortium received the FDA’s approval to start the clinical investigation of a novel therapeutic approach using a combination of three targeted therapies for the first line treatment of patients with advanced non small cell lung cancer. [WIN Consortium (Business Wire, Inc.)] Press Release

FDA Grants Orphan Drug Designation to Kadmon’s Tesevatinib for the Treatment of EGFR-Mutated Non-Small Cell Lung Cancer

Kadmon Holdings, Inc. announced that the FDA has granted orphan drug designation to tesevatinib, the company’s oral tyrosine kinase inhibitor, for the treatment of non-small cell lung cancer with epithelial growth factor receptor-activating mutations. [Kadmon Holdings, Inc.] Press Release

Thousands across India March in Support of Science

Thousands of scientists, university students and science enthusiasts gathered in dozens of Indian cities to march in support of science — lamenting their country’s low levels of funding for research, and complaining about government promotion of ‘unscientific ideas’. [Nature News] Editorial

FDA Cracks Down on Pioneering Doctor Who Created a Three-Parent Baby

The New York-based doctor who helped a couple have a child using DNA from three people has been told by the FDA that he can’t go ahead with clinical trials meant to test the technique. [MIT Technology Review] Editorial

CRISPR Patent Battle in Europe Takes a ‘Wild’ Twist with Surprising Player

MilliporeSigma, a subsidiary of pharmaceutical giant Merck KGaA of Darmstadt, Germany, has become a new major player in the complicated European patent battles over CRISPR, the revolutionary genome-editing tool. [ScienceInsider] Editorial

NEW EACR-MRS: Seed and Soil: In Vivo Models of Metastasis
November 27-29, 2017
Berlin, Germany

Visit our events page to see a complete list of events in the community.

NEW Physician Scientist or Senior Scientist – Pulmonary and Critical Care Medicine (Brigham and Women’s Hospital)

Postdoctoral Fellow – Pulmonary Research (University of Maryland)

Postdoctoral Position – Cardio/Pulmonary/Mitochondrial Research (University of Pittsburgh)

Faculty Position – Cancer Biology (Cold Spring Harbor Laboratory)

Clinical Research Fellow – Respiratory Medicine (University of Oxford)

Postdoctoral Position – Cell Signaling/Cancer Biology (Rutgers Cancer Institute of New Jersey)

Postdoctoral Fellow – Allergy and Immunology (New York University Medical Center)

Postdoctoral Fellow – Pathogenesis of Lung Diseases (Oklahoma State University)

Postdoctoral Fellow – Lung Microengineering (University of Colorado)

PhD Position – Lung Disease (Helmholtz Zentrum München)

Postdoctoral Associate – Lung Cancer Research (Weill Cornell Medicine)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Pulmonary Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.