Extracellular matrix-derived tripeptide proline-glycine-proline inhibits keratinocyte proliferation and migration.

Extracellular matrix-derived tripeptide proline-glycine-proline inhibits keratinocyte proliferation and migration.
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DOI:
10.1111/j.1524-475x.2011.00734.x
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发表时间:
2011-11
期刊:
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
影响因子:
--
通讯作者:
Kao WJ
Kao WJ
中科院分区:
其他
文献类型:
--
作者:
Ma Y;Kleinbeck K;Kao WJ

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角质形成细胞是表皮中的主要细胞类型,主要负责伤口愈合的上皮化阶段。本课题组前期研究表明IL-8浓度与猪皮肤二层创面延迟愈合呈正相关。 Interleukin-8 和胶原蛋白分解产物 N-乙酰基-脯氨酸-甘氨酸 (PGP) 被称为炎症期间中性粒细胞的趋化分子。两种分子的活性均依赖于趋化因子受体 CXCR1 和 CXCR2。除中性粒细胞外,角质形成细胞也表达 CXCR1 和 CXCR2。在这里,我们研究了 IL-8 和 PGP 对角质形成细胞增殖和迁移的影响。我们的结果表明,高达 100 ng/mL 的 IL-8 对角质形成细胞增殖或迁移没有任何显着影响。 ECM 衍生的三肽 PGP 趋化性地吸引中性粒细胞,但不吸引角质形成细胞。 PGP 以细胞类型特异性方式强烈抑制角质形成细胞增殖和迁移。因此,胶原蛋白分解产物 PGP 在调节伤口愈合的炎症和上皮化阶段中起着关键作用。
Keratinocytes are the predominant cell type in epidermis, and are primarily responsible for the epithelialization phase of wound healing. Previous studies by our group showed a positive correlation between IL-8 concentration and delayed healing of porcine cutaneous partial-thickness wounds. Interleukin-8 and collagen-breakdown product N-acetyl-Pro-Gly-Pro (PGP) are known as chemoattractant molecules for neutrophils during inflammation. The activity of both molecules is dependent on chemokine receptors CXCR1 and CXCR2. In addition to neutrophils, keratinocytes also express CXCR1 and CXCR2. Here we investigated the effects of IL-8 and PGP on keratinocyte proliferation and migration. Our results showed that IL-8 up to 100 ng/mL does not have any significant impact on keratinocyte proliferation or migration. ECM-derived tripeptide PGP chemotactically attracts neutrophils but not keratinocytes. PGP strongly inhibits keratinocyte proliferation and migration in a cell-type specific manner. Thus, collagen breakdown product PGP plays a key role in modulating both the inflammatory and epithelialization phases of wound healing.