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Platelet-derived transforming growth factor-β1 promotes keratinocyte proliferation in cutaneous wound healing.
Journal of Tissue Engineering and Regenerative Medicine ( IF 3.3 ) Pub Date : 2020-03-05 , DOI: 10.1002/term.3022
Deborah L W Chong 1 , Sarah Trinder 2 , Myriam Labelle 3 , Manuel Rodriguez-Justo 4 , Sian Hughes 4 , Alan M Holmes 2, 5 , Chris J Scotton 1, 6 , Joanna C Porter 1
Affiliation  

Platelets are a recognised potent source of transforming growth factor-β1 (TGFβ1), a cytokine known to promote wound healing and regeneration by stimulating dermal fibroblast proliferation and extracellular matrix deposition. Platelet lysate has been advocated as a novel personalised therapeutic to treat persistent wounds, although the precise platelet-derived growth factors responsible for these beneficial effects have not been fully elucidated. The aim of this study was to investigate the specific role of platelet-derived TGFβ1 in cutaneous wound healing. Using a transgenic mouse with a targeted deletion of TGFβ1 in megakaryocytes and platelets (TGFβ1fl/fl .PF4-Cre), we show for the first time that platelet-derived TGFβ1 contributes to epidermal and dermal thickening and cellular turnover after excisional skin wounding. In vitro studies demonstrate that human dermal fibroblasts stimulated with platelet lysate containing high levels of platelet-derived TGFβ1 did not exhibit enhanced collagen deposition or proliferation, suggesting that platelet-derived TGFβ1 is not a key promoter of these wound healing processes. Interestingly, human keratinocytes displayed enhanced TGFβ1-driven proliferation in response to platelet lysate, reminiscent of our in vivo findings. In summary, our novel findings define and emphasise an important role of platelet-derived TGFβ1 in epidermal remodelling and regeneration processes during cutaneous wound healing.

中文翻译:

血小板衍生的转化生长因子-β1促进皮肤伤口愈合中的角质形成细胞增殖。

血小板是公认的转化生长因子-β1 (TGFβ1) 的有效来源,TGFβ1 是一种已知通过刺激真皮成纤维细胞增殖和细胞外基质沉积来促进伤口愈合和再生的细胞因子。血小板裂解物被提倡作为一种新颖的个性化治疗剂来治疗持续性伤口,尽管负责这些有益作用的精确的血小板衍生生长因子尚未完全阐明。本研究的目的是研究血小板衍生的 TGFβ1 在皮肤伤口愈合中的特殊作用。使用在巨核细胞和血小板中靶向缺失 TGFβ1 (TGFβ1fl/fl.PF4-Cre) 的转基因小鼠,我们首次显示血小板衍生的 TGFβ1 有助于切除皮肤损伤后的表皮和真皮增厚和细胞更新。体外研究表明,用含有高水平血小板衍生 TGFβ1 的血小板裂解物刺激的人真皮成纤维细胞没有表现出增强的胶原沉积或增殖,这表明血小板衍生 TGFβ1 不是这些伤口愈合过程的关键促进剂。有趣的是,人类角质形成细胞显示出增强的 TGFβ1 驱动的增殖以响应血小板裂解物,这让人想起我们的体内研究结果。总之,我们的新发现定义并强调了血小板衍生的 TGFβ1 在皮肤伤口愈合过程中表皮重塑和再生过程中的重要作用。表明血小板衍生的 TGFβ1 不是这些伤口愈合过程的关键促进剂。有趣的是,人类角质形成细胞显示出增强的 TGFβ1 驱动的增殖以响应血小板裂解物,这让人想起我们的体内研究结果。总之,我们的新发现定义并强调了血小板衍生的 TGFβ1 在皮肤伤口愈合过程中表皮重塑和再生过程中的重要作用。表明血小板衍生的 TGFβ1 不是这些伤口愈合过程的关键促进剂。有趣的是,人类角质形成细胞显示出增强的 TGFβ1 驱动的增殖以响应血小板裂解物,这让人想起我们的体内研究结果。总之,我们的新发现定义并强调了血小板衍生的 TGFβ1 在皮肤伤口愈合过程中表皮重塑和再生过程中的重要作用。
更新日期:2020-04-22
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