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.
Molecular Histology and Cell Growth Unit, San Raffaele Scientific Institute, Milan, Italy. ranzato@unipmn.it
Elia
E
Ranzato
Simona
S
Martinotti
Andrea
A
Volante
Laura
L
Mazzucco
Bruno
B
Burlando
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