Involvement of PI3K and MMP1 in PDGF-induced Migration of Human Adipose-derived Stem Cells

Abstract

Human adult stem cells have widely been examined for their clinical application including their wound healing effect in vivo. To function as therapeutic cells, however, cells must represent the ability of directed migration in response to signals. This study aimed to investigate the mechanism of platelet-derived growth factor (PDGF)-induced migration of the human abdominal adipose-derived stem cells (hADSCs) in vitro. A general matrix metalloproteinase (MMP) inhibitor or a MMP2 inhibitor significantly inhibited the PDGF-induced migration. PDGF treatment exhibited greater mRNA level and denser protein level of MMP1. The conditioned medium of PDGF-treated cells showed a caseinolytic activity of MMP1. Transfection of cells with siRNA against MMP1 significantly inhibited MMP1 expression, its caseinolytic activity, and cell migration following PDGF treatment. Phosphatidylinositol 3-kinase (PI3K) inhibitor reduced the migration by about 50% without affecting ERK and MLC proteins. Rho-associated protein kinase inhibitor mostly abolished the migration and MLC proteins. The results suggest that PDGF might signal hADSCs through PI3K, and MMP1 activity could play an important role in this PDGF-induced migration in vitro.

Physical and Soluble Cues Enhance Tendon Progenitor Cell Invasion into Injectable Synthetic Hydrogels

“…[ 9c,15b ] Previous work has implicated increased matrix metalloproteinase (MMP) production, which facilitates extracellular matrix (ECM) degradation, in the mechanism of PDGF‐induced cell migration. [ 16 ] Therefore, our observation that solely PDGF‐BB induces TPC migration into MMP‐cleavable DexVS/VPMS hydrogels may stem from the nanoporosity of these materials, [ 10 ] which may necessitate matrix proteolysis and cytoskeletal remodeling distinct from the requirements for migration in 2D or in vivo settings. [ 17 ]…”

“…[9c,15b] Previous work has implicated increased matrix metalloproteinase (MMP) production, which facilitates extracellular matrix (ECM) degradation, in the mechanism of PDGF-induced cell migration. [16] Therefore, our observation that solely PDGF-BB induces TPC migration into MMP-cleavable DexVS/VPMS hydrogels may stem from the nanoporosity of these materials, [10] which may necessitate matrix proteolysis and cytoskeletal remodeling distinct from the requirements for migration in 2D or in vivo settings. [17] Since PDGF-BB has previously been demonstrated to act as both a chemokine and a mitogen, [18] we next investigated the extent to which these two distinct cell functions contributed to TPC outgrowth from spheroids in synthetic hydrogels.…”

A novel image analysis algorithm reveals that media conditioned with chitosan and platelet-rich plasma biomaterial dose dependently increases fibroblast migration in a scratch assay

“…´-100 10 plt ml 6 1 ). These concentrations are lower than most of those found in litterature when a single growth factor is used in a migration assay and that a dose effect is obtained [33,36]. This was not unexpected since the use of PRP allows for the delivery of a cocktail of GFs that can operate in synergy such as already observed with VEGF and PDGF in wound healing [37].…”

Effect and mechanisms of kaempferol against endometriosis based on network pharmacology and in vitro experiments

“…The downstream gene, PTEN, is downregulated in both eutopic and ectopic endometrium from patients with endometriosis [ 31 , 32 ]. Additionally, PTEN and platelet-derived growth factor (PDGF) play a role in the migration and invasion of endothelial cells and enhance the formation of ectopic lesions [ 33 ]. Migration and invasion are vital processes in the development and metastasis of cancer [ 34 , 35 ].…”