Arg-Gly-Asp-Ser (RGDS) peptide stimulates transforming growth factor beta1 transcription and secretion through integrin activation.
Extracellular matrix (ECM) components, through specific peptide motifs such as Arg-Gly-Asp (RGD), interact with integrins and can modify the behavior of cells. Transforming growth factor-beta1 (TGF-beta1) is the main cytokine involved in the synthesis of ECM proteins. We analyzed the effect of a RGD-containing peptide, as Arg-Gly-Asp-Ser (RGDS), on the regulation of TGF-beta1 secretion in cultured human mesangial cells. We found that RGDS increased mRNA expression and secretion of TGF-beta1 by stimulating the TGF-beta1 gene promoter. This effect was dependent on the interaction of RGDS with integrins. We evaluated the signaling pathways implicated in TGF-beta1 production by analyzing the effect of RGDS on kinase-related integrins. RGDS stimulated tyrosine phosphorylation as well as integrin-linked kinase (ILK) activity. However, tyrosine kinase inhibitors did not prevent the RGDS effect. In contrast, the inhibition of ILK by cell transfection with a kinase dead-ILK completely abolished the increased TGF-beta1 secretion and promoter activity in the presence of RGDS. Thus RGDS modulates the secretion of TGF-beta1, probably through increased synthesis by interacting with integrins and activating ILK. This supports a role for ECM components in the regulation of their own secretion.
Ortega-Velázquez
R
R
Department of Physiology, Alcalá University, Nephrology Section, Hospital Príncipe de Asturias, and IRSIN, Madrid, Spain.
Díez-Marqués
M L
ML
Ruiz-Torres
M P
MP
González-Rubio
M
M
Rodríguez-Puyol
M
M
Rodríguez Puyol
D
D
D002478:Cells, Cultured; D005920:Glomerular Mesangium / Q000166:cytology / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008954:Models, Biological; D009842:Oligopeptides / Q000494:pharmacology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014443:Tyrosine / Q000378:metabolism; D000099200:Scaffold Protein ILK
D016023:Integrins; D009842:Oligopeptides; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014443:Tyrosine; D000099200:Scaffold Protein ILK; C508960:TGFB1 protein, human; C046617:arginyl-glycyl-aspartyl-serine