FAM13A as potential therapeutic target in modulating TGF-β-induced airway tissue remodeling in COPD.

American Journal of Physiology. Lung Cellular and Molecular Physiology
Anthony TamChinten James Lim

Abstract

Genome-wide association studies have shown that a gene variant in the Family with sequence similarity 13, member A (FAM13A) is strongly associated with reduced lung function and the appearance of respiratory symptoms in patients with chronic obstructive pulmonary disease (COPD). A key player in smoking-induced tissue injury and airway remodeling is the transforming growth factor-β1 (TGF-β1). To determine the role of FAM13A in TGF-β1 signaling, FAM13A-/- airway epithelial cells were generated using CRISPR-Cas9, whereas overexpression of FAM13A was achieved using lipid nanoparticles. Wild-type (WT) and FAM13A-/- cells were treated with TGF-β1, followed by gene and/or protein expression analyses. FAM13A-/- cells augmented TGF-β1-induced increase in collagen type 1 (COL1A1), matrix metalloproteinase 2 (MMP2), expression compared with WT cells. This effect was mediated by an increase in β-catenin (CTNNB1) expression in FAM13A-/- cells compared with WT cells after TGF-β1 treatment. FAM13A overexpression was partially protective from TGF-β1-induced COL1A1 expression. Finally, we showed that airway epithelial-specific FAM13A protein expression is significantly increased in patients with severe COPD compared with control nonsmokers, and...Continue Reading

References

Aug 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·D C GruenertJ A Nadel
Jan 1, 1995·The European Respiratory Journal·P J VosC L van Herwaarden
Oct 6, 1998·Annual Review of Biochemistry·J Massagué
Dec 16, 1998·American Journal of Respiratory and Critical Care Medicine·W I de BoerJ H van Krieken
Dec 17, 2002·Journal of Cell Science·Justin P AnnesDaniel B Rifkin
Jul 10, 2003·Pulmonary Pharmacology & Therapeutics·Catherine DuvernelleNelly Frossard
Mar 6, 2004·Cancer Metastasis Reviews·Liliana Attisano, Etienne Labbé
Jun 25, 2004·The New England Journal of Medicine·James C HoggPeter D Paré
Jul 5, 2005·American Journal of Respiratory Cell and Molecular Biology·Rong D WangAndrew Churg
Nov 6, 2007·Journal of Korean Medical Science·Ju Hee KimDong-Gyu Kim
Dec 19, 2007·Respiratory Medicine·N MittmannJ M Fitzgerald
Mar 13, 2008·Structure·Yi XingWenqing Xu
Mar 22, 2008·Translational Research : the Journal of Laboratory and Clinical Medicine·Michelle Van ScoykRobert A Winn
Sep 9, 2009·Development·Renée van Amerongen, Roel Nusse
Feb 23, 2010·Nature Genetics·Michael H ChoEdwin K Silverman
Feb 26, 2010·Cold Spring Harbor Perspectives in Biology·Julian Heuberger, Walter Birchmeier
Mar 2, 2010·American Journal of Physiology. Lung Cellular and Molecular Physiology·Antonia P PopovaMarc B Hershenson
Jul 27, 2010·American Journal of Respiratory and Critical Care Medicine·Sreekumar G PillaiUNKNOWN ECLIPSE and ICGN Investigators
Sep 22, 2010·International Journal of Chronic Obstructive Pulmonary Disease·Kazuhito AsanoHiroaki Nakajima
Oct 5, 2010·American Journal of Respiratory and Critical Care Medicine·Nikolaus KneidingerMelanie Königshoff
Jun 11, 2011·International Journal of Chronic Obstructive Pulmonary Disease·Brian D KentWalter T McNicholas
Sep 13, 2011·American Journal of Physiology. Lung Cellular and Molecular Physiology·Hoeke A BaarsmaReinoud Gosens
Jan 5, 2013·Science·Le CongFeng Zhang
Jan 10, 2013·Human Genetics·Mateusz SiedlinskiUNKNOWN COPDGene and ECLIPSE Investigators
Mar 9, 2013·American Journal of Respiratory and Critical Care Medicine·Katrina SteilingMarc E Lenburg
Apr 19, 2013·Annals of the Rheumatic Diseases·Christian BeyerJörg H W Distler
Mar 14, 2014·The Lancet. Respiratory Medicine·Michael H ChoUNKNOWN NETT Genetics, ICGN, ECLIPSE and COPDGene Investigators
May 17, 2014·Nature Reviews. Drug Discovery·David CookMenelas N Pangalos
Jun 26, 2014·PloS One·Anthony TamDon D Sin
Nov 28, 2014·Respiratory Research·Jeanne-Marie PerotinGaëtan Deslee
Sep 26, 2015·The Lancet. Respiratory Medicine·Ma'en ObeidatPeter D Paré
Feb 11, 2016·American Journal of Respiratory and Critical Care Medicine·Zhiqiang JiangXiaobo Zhou
Feb 7, 2017·Nature Genetics·Brian D HobbsUNKNOWN International COPD Genetics Consortium
Dec 1, 2017·Journal of Cancer·Iwona Ziółkowska-SuchanekJerzy Nowak
Dec 15, 2017·Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society·Harriet CorvolLoic Guillot
Oct 10, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tao WangRakesh N Veedu
Apr 26, 2019·Nanoscale·Jayesh A KulkarniPieter R Cullis

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE7832
GSE37147

Methods Mentioned

BETA
ubiquitination
gene knockout
flow cytometry
PCR
confocal microscopy
transfections
transfection
transfect
flow

Software Mentioned

GraphPad Prism
Kaluza for Gallios
GraphPad
ImageJ

Related Concepts

Related Feeds

CRISPR Ribonucleases Deactivation

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on mechanisms that underlie deactivation of CRISPR ribonucleases. Here is the latest research.

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.