Involvement of β1-integrin via PIP complex and FAK/paxillin in dexamethasone-induced human mesenchymal stem cells migration.
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.
Yun
Seung Pil
SP
Department of Veterinary Physiology, College of Veterinary Medicine, Biotherapy Human Resources Center (BK21), Chonnam National University, Gwangju, Korea.
Ryu
Jung Min
JM
Han
Ho Jae
HJ
D000185:Actinin / Q000378:metabolism; D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D002465:Cell Movement / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D008840:Microfilament Proteins; D046912:Multiprotein Complexes / Q000378:metabolism*; D051419:Paxillin / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D000099200:Scaffold Protein ILK; D000096985:Calponins
D000185:Actinin; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D003907:Dexamethasone; D051417:Focal Adhesion Kinase 1; D019012:Integrin beta1; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D046912:Multiprotein Complexes; D051419:Paxillin; D017346:Protein Serine-Threonine Kinases; D011965:Receptors, Glucocorticoid; D000099200:Scaffold Protein ILK; C088088:LIMS1 protein, human; C486590:PARVA protein, human; D000096985:Calponins