瞬时受体电位香草酸 4 通过调节角质形成细胞和成纤维细胞迁移以及成纤维细胞中胶原蛋白的产生促进小鼠模型皮肤伤口愈合。

Transient receptor potential vanilloid 4 promotes cutaneous wound healing by regulating keratinocytes and fibroblasts migration and collagen production in fibroblasts in a mouse model.

机构信息

Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan.

出版信息

J Dermatol Sci. 2023 Nov;112(2):54-62. doi: 10.1016/j.jdermsci.2023.10.002. Epub 2023 Oct 11.

DOI:10.1016/j.jdermsci.2023.10.002

PMID:37839930

Abstract

BACKGROUND

Transient receptor potential vanilloid 4 (TRPV4), a cation ion channel, is expressed in different cells, and it regulates the development of different diseases. We recently found a high TRPV4 expression in the wounded skin area. However, the role of TRPV4 in cutaneous wound healing is unknown.

OBJECTIVE

To investigate the role of TRPV4 in cutaneous wound healing in a mouse model.

METHODS

Skin wound healing experiment and histopathological studies were performed between WT and TRPV4 KO mice. The effect of TRPV4 antagonist and agonist on cell migration, proliferation, and differentiation were examined in vitro.

RESULTS

TRPV4 expression was enhanced in wounded area in the skin. TRPV4 KO mice had impaired cutaneous wound healing compared with the WT mice. Further, they had significantly suppressed re-epithelialization and formation of granulation tissue, amount of collagen deposition, and number of α-SMA-positive myofibroblasts in skin wounds. qPCR revealed that the KO mice had decreased mRNA expression of COL1A1 and ACTA2 in skin wounds. In vitro, treatment with selective TRPV4 antagonist suppressed migrating capacity, scratch stimulation enhanced the expression of phospho-ERK in keratinocytes, and TGF-β stimulation enhanced the mRNA expression of COL1A1 and ACTA2 in fibroblasts. Selective TRPV4 agonist suppressed cell migration in keratinocytes, and did not enhance proliferation and migration, but promoted differentiation in fibroblasts.

CONCLUSION

TRPV4 mediates keratinocytes and fibroblasts migration and increases collagen deposition in the wound area, thereby promoting cutaneous wound healing.

摘要

背景

瞬时受体电位香草酸 4（TRPV4）是一种阳离子离子通道，在不同的细胞中表达，调节着不同疾病的发展。我们最近发现 TRPV4 在受伤皮肤区域高表达。然而，TRPV4 在皮肤伤口愈合中的作用尚不清楚。

目的

在小鼠模型中研究 TRPV4 在皮肤伤口愈合中的作用。

方法

在 WT 和 TRPV4 KO 小鼠之间进行皮肤伤口愈合实验和组织病理学研究。在体外检查 TRPV4 拮抗剂和激动剂对细胞迁移、增殖和分化的影响。

结果

TRPV4 在受伤区域的皮肤中表达增强。与 WT 小鼠相比，TRPV4 KO 小鼠的皮肤伤口愈合受损。此外，它们的上皮化和肉芽组织形成、胶原蛋白沉积量以及皮肤伤口中α-SMA 阳性肌成纤维细胞数量明显减少。qPCR 显示 KO 小鼠皮肤伤口中 COL1A1 和 ACTA2 的 mRNA 表达减少。在体外，选择性 TRPV4 拮抗剂处理抑制了角质形成细胞的迁移能力，划痕刺激增强了角质形成细胞中磷酸化-ERK 的表达，TGF-β 刺激增强了成纤维细胞中 COL1A1 和 ACTA2 的 mRNA 表达。选择性 TRPV4 激动剂抑制了角质形成细胞的迁移，并且不会增强增殖和迁移，但促进了成纤维细胞的分化。