Secreted PEDF modulates fibroblast collagen synthesis through M1 macrophage polarization under expanded condition - 18/09/21
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Abstract |
Tissue expansion is widely used to obtain new skin tissue for repairing defects in the clinical practice of plastic surgery. One major complication can be dermal thinning during expansion, which usually leads to skin rupture. Collagen synthesis can determine dermal thickness and can be influenced by macrophage polarization during expansion. The aim of the study was to test whether pigment epithelium-derived factor (PEDF) could be a modulator of collagen synthesis in fibroblasts by regulating macrophage polarization during skin expansion. Our results showed that PEDF mRNA expression was increased in expanded human and mouse epidermis. PEDF protein levels were elevated in the subcutaneous exudates of a rat skin expansion model. Increased PEDF mRNA expression was accompanied by dermal thinning during a three-week expansion protocol. Subcutaneous injection of PEDF in vivo further resulted in dermal thinning and cell number increase of M1 macrophage in the expanded skin. PEDF also promoted macrophage polarization in vitro to the M1 subtype under hypoxic conditions. PEDF did not influence collagen gene expression in fibroblasts directly, but attenuated collagen synthesis in a macrophage-mediated manner. Additionally, blockage of PEDF receptors on macrophages with inhibitors rescued collagen synthesis in fibroblasts. Our research demonstrated PEDF elevation in expanded skin leads to dermal thinning through M1 macrophage-mediated collagen synthesis inhibition in fibroblasts. Our results could form a basis for the development of novel strategies to improve skin integrity in expanded skin by using PEDF.
Le texte complet de cet article est disponible en PDF.Highlights |
• | Dermal thinning during tissue expansion leads to skin rupture. |
• | PEDF is up-regulated and secreted in the expanded epidermis. |
• | PEDF inhibits the collagen synthesis via polarizing macrophages to M1 subtype, thus leading to dermal thinning. |
• | Inhibiting the activity of PEDF receptors can increase the expression of collagens in fibroblasts. |
• | PEDF might be a potential therapy target for dermal thinning during skin expansion. |
Abbreviations : PEDF, ECM, H&E, BSA, TcPO2,, qPCR, TNF-α, IL, iNOS, Arg-1, ATGL, LR, BEL
Keywords : Skin expansion, Hypoxia, PEDF, Macrophage polarization, Dermal thinning
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Vol 142
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