Selective integrin subunit reduction disrupts fibronectin extracellular matrix deposition and fibrillin 1 gene expression.
Integrins are transmembrane receptors that can specifically bind extracellular matrix (ECM) proteins. Assembly of the ECM protein fibronectin into fibrils has been shown to be a cell-mediated process that requires integrins. Like fibronectin, fibrillin 1 is an ECM glycoprotein that can assemble into fibrils, but the role of integrins in fibril formation is not understood. To investigate the role of integrins in fibrillin 1 ECM deposition, cells that normally produce and assemble fibrillin 1 fibers in vitro were stably transfected with plasmid constructs encoding short interfering RNAs that target specific integrin subunits. Cells that were deficient in α2- and β3-integrin subunits produced and deposited fibronectin normally, but cells that were deficient for α5 and αV were unable to elaborate a fibronectin matrix, although they continued to produce and secrete the protein. Surprisingly, the cells that were unable to elaborate a fibronectin matrix also lost fibrillin 1 gene expression.
Division of Musculoskeletal Sciences, Department of Orthopaedics, Penn State College of Medicine, Hershey, PA 17033, USA. rajeev04mys@yahoo.com
Rajeev K
RK
Boregowda
Brooke M
BM
Krovic
Timothy M
TM
Ritty
D002448:Cell Adhesion; D045744:Cell Line, Tumor; D005109:Extracellular Matrix / Q000378:metabolism*; D000071838:Fibrillin-1; D000071837:Fibrillins; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D039421:Integrin alpha2 / Q000235:genetics / Q000378:metabolism; D039482:Integrin alpha5 / Q000235:genetics / Q000378:metabolism; D039564:Integrin alphaV / Q000235:genetics / Q000378:metabolism; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism; D016023:Integrins; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism; D034741:RNA, Small Interfering; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism; D054392:Adipokines
D000071838:Fibrillin-1; D000071837:Fibrillins; D005353:Fibronectins; D039421:Integrin alpha2; D039482:Integrin alpha5; D039564:Integrin alphaV; D039661:Integrin beta3; D016023:Integrins; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; C000605722:FBN1 protein, human; D054392:Adipokines