Platelets Regulate the Migration of Keratinocytes via Podoplanin/CLEC-2 Signaling during Cutaneous Wound Healing in Mice

被引：35

作者：

Asai, Jun ^{[1
]}

Hirakawa, Satoshi ^{[3
]}

Sakabe, Jun-ichi ^{[3
]}

Kishida, Tsunao ^{[2
]}

Wada, Makoto ^{[1
]}

Nakamura, Naomi ^{[1
]}

Takenaka, Hideya ^{[1
]}

Mazda, Osam ^{[2
]}

Urano, Tetsumei ^{[4
]}

Suzuki-Inoue, Katsue ^{[5
]}

Tokura, Yoshiki ^{[3
]}

Katoh, Norito ^{[1
]}

机构：

[1] Kyoto Prefectural Univ Med, Dept Dermatol, Kyoto 6028566, Japan

[2] Kyoto Prefectural Univ Med, Dept Immunol, Kyoto 6028566, Japan

[3] Hamamatsu Univ Sch Med, Dept Dermatol, Hamamatsu, Shizuoka 4313192, Japan

[4] Hamamatsu Univ Sch Med, Dept Physiol, Hamamatsu, Shizuoka 4313192, Japan

[5] Univ Yamanashi, Fac Med, Dept Clin & Lab Med, Kofu, Yamanashi, Japan

来源：

AMERICAN JOURNAL OF PATHOLOGY | 2016年 / 186卷 / 01期

关键词：

SQUAMOUS-CELL CARCINOMAS; AGGREGATION-INDUCING FACTOR; RECEPTOR CLEC-2; EXPRESSION; ACTIVATION; INVOLVEMENT; GENE;

D O I：

10.1016/j.ajpath.2015.09.007

中图分类号：

R36 [病理学];

学科分类号：

100103 [病原生物学];

摘要：

Podoplanin is an endogenous ligand for C-type lectin-like receptor 2 (CLEC-2), which is expressed on platelets. Recent evidence indicates that this specific marker of Lymphatic endothelial cells is also expressed by keratinocytes at the edge of wounds. However, whether podoplanin or platelets play a role in keratinocyte activity during wound healing remains unknown. We evaluated the effect of podoplanin expression levels on keratinocyte motility using cultured primary normal human epidermal keratinocytes (NHEKs). Down-regulation of podoplanin in NHEKs via transfection with podoplanin siRNA inhibited their migration, indicating that podoplanin plays a mandatory role in this process. In addition, down-regulation of podoplanin was correlated with up-regulation of E-cadherin, suggesting that podoplanin-mediated stimulation of keratinocyte migration is associated with a toss of E-cadherin. Both the addition of platelets and treatment with CLEC-2 inhibited the migration of NHEKs. The down-regulation of RhoA activity and the up-regulation of E-cadherin in keratinocytes were also induced by CLEC-2. In conclusion, these results suggest that podoplanin/CLEC-2 signaling regulates keratinocyte migration via modulating E-cadherin expression through RhoA signaling. Altering the regulation of keratinocyte migration by podoplanin might be a novel therapeutic approach to improve wound healing.

引用

页码：101 / 108

页数：8

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