Abstract
IntroductionMesenchymal stem cells (MSC) are well described for their role in tissue regeneration following injury. Migratory properties of endogenous or administrated MSC are critical for tissue repair processes. Platelet-derived growth factor (PDGF) is a chemotactic growth factor that elicits mesenchymal cell migration. However, it is yet to be elucidated if signaling pathways other than direct activation of PDGF receptor (PDGF-R) are involved in PDGF-induced cell migration.MethodsKnocking down and co-immunoprecipitation approaches were used to evaluate urokinase-type plasminogen activator receptor (uPAR) requirement and its interactions with proteins involved in migration mechanisms, in human MSC induced to migrate under PDGF-AB effect.ResultsWe demonstrated that uPAR activation and its association with β1-integrin are required for PDGF-AB-induced migration. This phenomenon takes place in MSC derived from bone marrow and from adipose tissue.ConclusionsWe showed that PDGF-AB downstream signaling requires other effector molecules in MSC such as the uPA/uPAR system and β1 integrin signaling pathway known for their role in migration. These findings provide new insights in molecular mechanisms of PDGF-AB-induced migration of human MSC that may be relevant to control MSC function and tissue remodeling after injury.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-015-0163-5) contains supplementary material, which is available to authorized users.
Highlights
Mesenchymal stem cells (MSC) are well described for their role in tissue regeneration following injury
We demonstrated that urokinase-type plasminogen activator receptor (uPAR) activation and its association with β1-integrin are required for Platelet-derived growth factor (PDGF)-AB-induced migration
We showed that PDGF-AB downstream signaling requires other effector molecules in MSC such as the urokinase-type plasminogen activator (uPA)/uPAR system and β1 integrin signaling pathway known for their role in migration
Summary
Mesenchymal stem cells (MSC) are well described for their role in tissue regeneration following injury. Chabot et al Stem Cell Research & Therapy (2015) 6:188 tissue repair [14], but Ponte et al [12] showed that TNFα does not enhance MSC migration towards PDGF. In both mouse and human, the PDGFs consist of four inactive monomeric ligands (A–D) that assemble into biologically active homodimers; only PDGF-A and PDGF-B can form functional heterodimers. PDGF-AA and PDGF-BB cell signaling has been well described on migration of cells of mesenchymal origin [14, 15], less is known about the effects of PDGF-AB. PDGF-AB was shown to promote human MSC migration [12, 17], but many questions related to the molecular mechanisms underlying its effects remain largely unanswered
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