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  • Title: Involvement of β1-integrin via PIP complex and FAK/paxillin in dexamethasone-induced human mesenchymal stem cells migration.
    Author: Yun SP, Ryu JM, Han HJ.
    Journal: J Cell Physiol; 2011 Mar; 226(3):683-92. PubMed ID: 20717960.
    Abstract:
    Although glucocorticoids strongly affect numerous biological processes including cell growth, development, and homeostasis, their effects on migration of human mesenchymal stem cells (hMSCs) are unclear. Therefore, we investigated the role of dexamethasone (DEX) and its related signaling pathways on migration of hMSCs. We found that DEX, at 10(-8) to 10(-6) M, significantly increased migration after a 24 h incubation, and DEX (10(-6) M) increased migration at >12 h. Moreover, DEX (10(-6) M) increased the level of glucocorticoid receptor (GR)-α mRNA and protein expression, but not GR-β mRNA. The increases in DEX-induced migration were inhibited by the GR antagonist mifepristone (10(-7) M). In addition, DEX increased integrin-linked kinase (ILK) and α-parvin expression but did not change PINCH-1/2 expression in lysate. DEX also increased formations of complex with ILK and α-parvin, and ILK and PINCH-1/2 as shown by immunoprecipitation, which were all inhibited by mifepristone. DEX-induced migration was blocked by ILK and α-parvin small interfering(si)RNAs. In addition, DEX increased focal adhesion kinase (FAK) and paxillin expression, which were attenuated by ILK and α-parvin siRNAs. DEX-induced cell migration was inhibited by FAK/paxillin siRNAs. DEX also increased β1-integrin expression, which was blocked by FAK/paxillin siRNAs. In addition, DEX-induced cell migration was inhibited by β1-integrin siRNA. Downregulation of ILK, α-parvin, FAK/paxillin and β1-integrin expression by siRNAs decreased DEX-induced filamentous(F)-actin organization and migration of hMSCs. In conclusion, DEX partially stimulates hMSC migration by the expression of β1-integrin through formation of a PINCH-1/2/ILK/α-parvin complex (PIP complex), and FAK and paxillin expression.
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