Transforming growth factor-beta (TGF-beta) stimulates the expression of beta1 integrins and adhesion by rat mesangial cells.
Transforming growth factor-beta (TGF-beta) has been implicated in the pathogenesis of mesangial matrix (MM) accumulation in human and experimental glomerulonephritis. To clarify molecular mechanisms responsible for pathological MM deposition, we examined the effect of TGF-beta on the production of beta1 integrins and on adhesion function of rat mesangial cells (MC). In immunoprecipitation experiments using [35S]methionine-labeled MC, stimulation of MC with TGF-beta for 48 h resulted in an increase in the synthesis of alpha1beta1 (collagen/laminin receptor) and alpha5beta1 (fibronectin receptor) integrins accompanied by increases in the synthesis of their ligands, collagen type I (collagen I), and fibronectin. A time-dependent increase in beta1, alpha1 integrin subunit mRNA peaking 48 h after exposure to TGF-beta was shown by Northern blot analysis. After 48 h of treatment with TGF-beta, MC displayed significant increases in adhesion to fibronectin, collagen I, and laminin as compared to untreated MC. Anti-beta1 antiserum significantly inhibits MC adhesion to fibronectin, collagen I, and laminin. Anti-alpha1 subunit antibody very strongly inhibited adhesion to collagen I and laminin, but not to fibronectin. Synthetic peptides containing RGD sequences specifically blocked adhesion to fibronectin. These data suggest that TGF-beta may promote MM deposition by increasing MC synthesis of both matrix proteins and beta1 integrins which facilitate binding of these proteins to the MC surface and thus enhance their incorporation into MM.
Kagami
S
S
Department of Pediatrics, School of Medicine, University of Tokushima, Japan.
Kuhara
T
T
Yasutomo
K
K
Okada
K
K
Löster
K
K
Reutter
W
W
Kuroda
Y
Y
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D019012:Integrin beta1 / Q000096:biosynthesis* / Q000302:isolation & purification; D007797:Laminin; D008024:Ligands; D009842:Oligopeptides; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D019012:Integrin beta1; D007797:Laminin; D008024:Ligands; D009842:Oligopeptides; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003094:Collagen; C058161:glycyl-arginyl-glycyl-aspartyl-seryl-proline; C058347:glycyl-arginyl-glycyl-glutamyl-seryl-proline