Platelet lysate modulates MMP-2 and MMP-9 expression, matrix deposition and cell-to-matrix adhesion in keratinocytes and fibroblasts.
Cell-matrix interactions are an essential element of wound healing, while platelet derivatives are used in clinical settings for the treatment of chronic wounds. We used a platelet lysate (PL), which had been previously shown to accelerate in vitro the wounding of HaCaT keratinocytes and fibroblasts (J Cell Mol Med, 13, 2009, 2030; Br J Dermatol, 159, 2008, 537), to study the modulation of MMP-2 and MMP-9 collagenase expression, collagen type I and III production and syndecan-4 expression and rearrangement in these cells. Zymography and Western blot analyses showed that exposure to 20% (v/v) PL for 24 h induced an apparently ERK1/2- and p38-dependent, NF-kappaB-independent, translational upregulation of MMP-9 in HaCaT, while HaCaT MMP-2 and fibroblast collagenases were almost unaffected. The use of in-cell ELISA showed that PL induced an increase in the collagen III production of fibroblasts. In-cell ELISA and immunofluorescence microscopy revealed an increase in the expression of syndecan-4 and its rearrangement to form focal adhesions in both cell types after PL exposure. Taken together, data indicate that PL promotes keratinocyte epithelialization and regulates fibroblast matrix deposition, thus providing a molecular basis for the ability of this platelet derivative to heal severe and problematic wounds without leading to heavy scarring and keloid formation.
Ranzato
Elia
E
Molecular Histology and Cell Growth Unit, San Raffaele Scientific Institute, Milan, Italy. ranzato@unipmn.it
Martinotti
Simona
S
Volante
Andrea
A
Mazzucco
Laura
L
Burlando
Bruno
B
D000704:Analysis of Variance; D001792:Blood Platelets / Q000378:metabolism* / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism* / Q000502:physiology; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D053671:Syndecan-4 / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
D024042:Collagen Type I; D024061:Collagen Type III; D016328:NF-kappa B; D053671:Syndecan-4; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9