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P2X7受体对人角质形成细胞和真皮成纤维细胞增殖与迁移的差异作用

Differential Effect of P2X7 Receptors on Proliferation and Migration of Human Keratinocytes and Dermal Fibroblasts.

作者信息

Soszyńska Marta, Komorowski Michał, Łuszczyński Krzysztof, Radziszewski Marcin, Krześniak Natalia, Shevchenko Katerina, Górecki Dariusz C, Malejczyk Jacek, Ścieżyńska Aneta

机构信息

Department of Histology and Embryology, Medical University of Warsaw, 02-004 Warsaw, Poland.

Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine National Research Institute, 128 Szaserów Street, 04-141 Warsaw, Poland.

出版信息

Int J Mol Sci. 2025 Sep 3;26(17):8548. doi: 10.3390/ijms26178548.

Abstract

Purinergic P2X7 receptors are involved in cellular processes such as inflammation, proliferation, and tissue remodeling, although their significance in human skin physiology remains poorly understood. In this study, we demonstrated strong P2X7 receptor immunoreactivity in the basal and granular layers of the epidermis. Cutaneous expression of P2X7 receptors was further confirmed at the level of specific mRNA and protein in cultured primary human keratinocytes and dermal fibroblasts. To reveal a possible role of these receptors in regulation of keratinocyte and fibroblast function, the cells were treated with a P2X7 agonist BzATP, or its selective antagonist A438079. Cell proliferation and viability were assessed using an immunofluorescence-based cell counter, and cell migration was evaluated by wound healing assay. P2X7 stimulation with BzATP significantly inhibited keratinocyte proliferation and migration, while P2X7 inhibition with A438079 significantly enhanced keratinocyte migration. In contrast, fibroblasts displayed minimal response to either treatment. These findings indicate that P2X7 regulates keratinocyte growth, and purinergic signaling may play a role in the skin. Our data also suggest that selective P2X7 inhibition may support re-epithelialization under conditions associated with impaired wound healing.

摘要

嘌呤能P2X7受体参与炎症、增殖和组织重塑等细胞过程,尽管其在人类皮肤生理学中的意义仍知之甚少。在本研究中,我们证明了表皮基底层和颗粒层中存在强烈的P2X7受体免疫反应性。在培养的原代人角质形成细胞和真皮成纤维细胞中,通过特异性mRNA和蛋白质水平进一步证实了P2X7受体的皮肤表达。为了揭示这些受体在调节角质形成细胞和成纤维细胞功能中的可能作用,用P2X7激动剂BzATP或其选择性拮抗剂A438079处理细胞。使用基于免疫荧光的细胞计数器评估细胞增殖和活力,并通过伤口愈合试验评估细胞迁移。用BzATP刺激P2X7可显著抑制角质形成细胞的增殖和迁移,而用A438079抑制P2X7可显著增强角质形成细胞的迁移。相比之下,成纤维细胞对任何一种处理的反应都很小。这些发现表明P2X7调节角质形成细胞的生长,嘌呤能信号可能在皮肤中发挥作用。我们的数据还表明,在伤口愈合受损的情况下,选择性抑制P2X7可能有助于再上皮化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6341/12429528/b9c03680d14f/ijms-26-08548-g001.jpg

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