CFTR dysfunction increases endoglin and TGF-β signaling in airway epithelia

Physiological Reports
Teodora NicolaWilliam T Harris

Abstract

Endoglin (ENG) regulates signaling by transforming growth factor-β (TGF-β), a genetic modifier of cystic fibrosis (CF) lung disease severity. We hypothesized that ENG mediates TGF-β pathobiology in CF airway epithelia. Comparing CF and non-CF human lungs, we measured ENG by qPCR, immunoblotting and ELISA. In human bronchial epithelial cell lines (16HBE), we used CFTR siRNA knockdown and functional inhibition (CFTRINH -172) to connect loss of CFTR to ENG synthesis. Plasmid overexpression of ENG assessed the direct effect of ENG on TGF-β transcription and signal amplification in 16HBE cells. We found ENG protein to be increased more than fivefold both in human CF bronchoalveolar fluid (BALF) and human CF lung homogenates. ENG transcripts were increased threefold in CF, with a twofold increase in TGF-β signaling. CFTR knockdown in 16HBE cells tripled ENG transcription and doubled protein levels with corresponding increases in TGF-β signaling. Plasmid overexpression of ENG alone nearly doubled TGF-β1 mRNA and increased TGF-β signaling in 16HBE cells. These experiments identify that loss of CFTR function increases ENG expression in CF epithelia and amplifies TGF-β signaling. Targeting ENG may offer a novel therapeutic opportunity to...Continue Reading

References

May 23, 2001·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·A Rodríguez-PeñaJ M López-Novoa
Nov 2, 2002·Hypertension·Ana Rodríguez-PeñaJosé M López-Novoa
Dec 17, 2002·Journal of Cell Science·Justin P AnnesDaniel B Rifkin
May 4, 2004·Methods : a Companion to Methods in Enzymology·Brian DalbyValentina C Ciccarone
May 13, 2005·The New England Journal of Medicine·Steven M RoweEric J Sorscher
Oct 7, 2005·The New England Journal of Medicine·Mitchell L DrummUNKNOWN Gene Modifier Study Group
Jan 31, 2006·Journal of Physiology and Biochemistry·M PrietoN Eleno
Nov 29, 2007·Pediatric Research·Namasivayam AmbalavananYiu-Fai Chen
Jan 31, 2008·JAMA : the Journal of the American Medical Association·J Michael CollacoGarry R Cutting
Feb 28, 2008·Journal of Cell Science·Soraya VelascoAlicia Rodríguez-Barbero
May 20, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·Namasivayam AmbalavananYiu-Fai Chen
Sep 25, 2008·Current Opinion in Pulmonary Medicine·Joseph M Collaco, Garry R Cutting
Mar 10, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Teodora NicolaNamasivayam Ambalavanan
Apr 22, 2009·Pediatric Pulmonology·Stacey L Peterson-CarmichaelStephanie D Davis
May 3, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Teodora NicolaYiu-Fai Chen
Jun 17, 2011·Nature·Minlong ShiTimothy A Springer
Jan 31, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Nelida OlaveNamasivayam Ambalavanan
Jul 7, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Lee S RosenMichael S Gordon
Sep 21, 2012·Nature Reviews. Molecular Cell Biology·Joan Massagué
Jan 22, 2014·Current Oncology Reports·Lee S RosenDaniela E Matei
Apr 25, 2014·British Journal of Pharmacology·N MelisC Duranton
Sep 28, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michael S GordonLee S Rosen
Jan 22, 2015·The New England Journal of Medicine·David A StoltzMichael J Welsh
May 12, 2015·Matrix Biology : Journal of the International Society for Matrix Biology·Boris Hinz
Dec 13, 2017·American Journal of Respiratory and Critical Care Medicine·Farruk Lutful KabirWilliam T Harris

❮ Previous
Next ❯

Citations

Sep 18, 2020·International Journal of Molecular Sciences·Luís SousaMargarida D Amaral

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
bronchoalveolar lavage
ELISA
transfection

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Mirjana Jerkic, Michelle Letarte
The Annals of Otology, Rhinology, and Laryngology
B F McCabe
The Journal of Investigative Dermatology
Eduardo Pérez-GómezJosé M López-Novoa
The Annals of Otology, Rhinology, and Laryngology
B F McCabe
© 2022 Meta ULC. All rights reserved