Focal Adhesion Kinase Regulates Fibroblast Migration via Integrin beta-1 and Plays a Central Role in Fibrosis

Scientific Reports
Xue-Ke ZhaoQuan Zhang

Abstract

Lung fibrosis is a major medical problem for the aging population worldwide. Fibroblast migration plays an important role in fibrosis. Focal Adhesion Kinase (FAK) senses the extracellular stimuli and initiates signaling cascades that promote cell migration. This study first examined the dose and time responses of FAK activation in human lung fibroblasts treated with platelet derived growth factor BB (PDGF-BB). The data indicate that FAK is directly recruited by integrin β1 and the subsequent FAK activation is required for fibroblast migration on fibronectin. In addition, the study has identified that α5β1 and α4β1 are the major integrins for FAK-mediated fibroblast migration on fibronect. In contrast, integrins αvβ3, αvβ6, and αvβ8 play a minor but distinct role in fibroblast migration on fibronectin. FAK inhibitor significantly reduces PDGF-BB stimulated fibroblast migration. Importantly, FAK inhibitor protects bleomycin-induced lung fibrosis in mice. FAK inhibitor blocks FAK activation and significantly reduces signaling cascade of fibroblast migration in bleomycin-challenged mice. Furthermore, FAK inhibitor decreases lung fibrotic score, collagen accumulation, fibronectin production, and myofibroblast differentiation in in b...Continue Reading

References

Aug 1, 1976·Environmental Health Perspectives·I Y Adamson
Sep 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·S K HanksS K Patel
Jan 1, 1982·Methods in Enzymology·R A Berg
Aug 14, 1999·Science·F G Giancotti, E Ruoslahti
Oct 3, 1999·Physiological Reviews·C H Heldin, B Westermark
May 12, 2000·Nature Cell Biology·D J SiegD D Schlaepfer
May 19, 2000·The Biochemical Journal·A L Bishop, A Hall
Jun 20, 2001·The Journal of Clinical Investigation·J F PittetD Sheppard
Oct 6, 2001·American Journal of Respiratory and Critical Care Medicine·T E KingR M Cherniack
Nov 27, 2001·Science·E CukiermanK M Yamada
Mar 18, 2003·Journal of Cell Science·J Thomas Parsons
Apr 19, 2003·The Journal of Biological Chemistry·Jinbin ZhaiDavid D Schlaepfer
Dec 4, 2003·Thrombosis and Haemostasis·Boris Hinz, Giulio Gabbiani
Jan 15, 2004·The Journal of Clinical Investigation·Harold A Chapman
Apr 28, 2004·Current Opinion in Genetics & Development·David D Schlaepfer, Satyajit K Mitra
Jun 19, 2004·American Journal of Respiratory Cell and Molecular Biology·Andrew M TagerAndrew D Luster
Jul 21, 2004·The Journal of Cell Biology·Michael D Schaller
Sep 21, 2005·American Journal of Respiratory Cell and Molecular Biology·Michael A Matthay, Guy A Zimmerman
Jun 3, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Priscila M F Siesser, Steven K Hanks
Jul 11, 2006·Journal of Cellular Biochemistry·Braden D CoxCandece L Gladson
Jun 15, 2007·International Journal of Cancer. Journal International Du Cancer·Teresa CabezónNoona Ambartsumian
Aug 9, 2007·Proceedings of the American Thoracic Society·Roland M du Bois
Nov 13, 2007·American Journal of Physiology. Lung Cellular and Molecular Physiology·Bethany B Moore, Cory M Hogaboam
May 24, 2008·The Journal of Biological Chemistry·Bin ShanJoseph A Lasky
Dec 1, 2009·Cell·Jean Paul ThieryM Angela Nieto
Dec 19, 2009·Scandinavian Journal of Gastroenterology·Norman J HacklInaam A Nakchbandi
Dec 19, 2009·The American Journal of Pathology·Kjetil Boye, Gunhild M Maelandsmo
Jun 22, 2010·American Journal of Physiology. Lung Cellular and Molecular Physiology·Amber L DegryseWilliam E Lawson
Jun 29, 2011·The Journal of Experimental Medicine·Yuejuan LiPaul W Noble
Jan 25, 2012·The Journal of Cell Biology·Christine LawsonDavid D Schlaepfer
Mar 14, 2012·Integrative Biology : Quantitative Biosciences From Nano to Macro·Jenna L BalestriniBoris Hinz
Jul 28, 2012·Current Molecular Medicine·R DonatoC L Geczy
Mar 19, 2013·The American Journal of Pathology·Qiang DingMitchell A Olman

❮ Previous
Next ❯

Citations

Oct 4, 2016·Journal of Tissue Engineering and Regenerative Medicine·Owen G DaviesYang Liu
Mar 10, 2017·Expert Review of Respiratory Medicine·Ioannis P TomosSpyros A Papiris
May 28, 2017·Experimental Biology and Medicine·Karen M Doersch, M Karen Newell-Rogers
Jan 16, 2018·The Journal of International Medical Research·Tao TianYu-Juan Yang
Aug 15, 2018·The Journal of Bone and Joint Surgery. American Volume·Masamitsu HaraSeiji Okada
Jan 20, 2018·Current Rheumatology Reports·Alba Santos, David Lagares
Oct 11, 2019·Cell Biochemistry and Biophysics·John J EvansPeter H Sykes
Mar 17, 2020·Cancer Biology & Therapy·Nefeli ZacharopoulouChristos Stournaras
Jul 30, 2018·Journal of Mammary Gland Biology and Neoplasia·Ethan J BrockBonnie F Sloane
Nov 30, 2018·Frontiers in Immunology·Arjan van CaamPeter van der Kraan
May 31, 2019·Journal of Cellular Biochemistry·Yongchao DuXiang Chen
Aug 8, 2020·Proceedings of the National Academy of Sciences of the United States of America·Lynn M WilliamsJagdeep Nanchahal
Jan 17, 2020·Scientific Reports·Mingxing FangZhiyong Wang
Apr 1, 2017·Frontiers in Physiology·Priscila J CarneiroFernanda F Cruz
Apr 19, 2017·Cell Death Discovery·Jaymin J KathiriyaVrushank Davé
May 20, 2019·Journal of Cellular Biochemistry·Hengting XiaoYing Li
Oct 13, 2020·Frontiers in Pharmacology·Javad Sharifi-RadNatália Martins
Dec 3, 2020·Drug Design, Development and Therapy·Chengkuan SunJing Sun
Mar 17, 2021·Biomaterials Science·Sitara VedaramanLaura De Laporte
Feb 3, 2018·Journal of Proteome Research·Justin D La FavorArthur L Burnett
Aug 28, 2021·Biomolecules·Cian D'Arcy, Christina Kiel
Sep 22, 2021·Advances in Wound Care·Artem A TrotsyukGeoffrey C Gurtner

❮ Previous
Next ❯

Methods Mentioned

BETA
pull-down
GTPases
motility assay

Software Mentioned

SPSS
Sigma Plot
Adobe Photoshop

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.