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Arg-Gly-Asp-Ser (RGDS) Peptide Stimulates Transforming Growth Factor beta1 Transcription and Secretion Through Integrin Activation

Arg-Gly-Asp-Ser (RGDS) Peptide Stimulates Transforming Growth Factor beta1 Transcription and Secretion Through Integrin Activation

R Ortega-Velázquez, M L Díez-Marqués, M P Ruiz-Torres, M González-Rubio, M Rodríguez-Puyol, D Rodríguez Puyol

FASEB J. 2003 Aug;17(11):1529-31.

PMID: 12824296

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP91037659	Arg-Gly-Asp-Ser		91037-65-9	Price

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