4.7 Review

The Role of Podoplanin in Skin Diseases

Journal

Publisher

MDPI
DOI: 10.3390/ijms23031310

Keywords

podoplanin; psoriasis; wound healing; melanoma; squamous cell carcinoma; extramammary Paget's disease

Funding

  1. [25461674]
  2. [19K08753]

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Podoplanin is a glycoprotein receptor that is highly expressed in normal skin and plays a crucial role in various pathological skin conditions, including psoriasis, chronic inflammation, wound healing, and skin cancer. It is involved in epidermal hyperproliferation, IL-17 secretion, re-epithelialization, and tumor cell migration and epithelial-mesenchymal transition. In addition, its expression in peritumoral cells can predict aggressive behavior and poor prognosis.
Podoplanin is a sialomucin-like type I transmembrane receptor glycoprotein that is expressed specifically in lymphatic vessels, sebaceous glands, and hair follicles in normal skin. However, under pathological conditions podoplanin expression is upregulated in various cells, such as keratinocytes, fibroblasts, tumor cells, and inflammatory cells, and plays pivotal roles in different diseases. In psoriasis, podoplanin expression is induced in basal keratinocytes via the JAK-STAT pathway and contributes toward epidermal hyperproliferation. Podoplanin expression on keratinocytes can also promote IL-17 secretion from lymphocytes, promoting chronic inflammation. During wound healing, the podoplanin/CLEC-2 interaction between keratinocytes and platelets regulates re-epithelialization at the wound edge. In skin cancers, podoplanin expresses on tumor cells and promotes their migration and epithelial-mesenchymal transition, thereby accelerating invasion and metastasis. Podoplanin is also expressed in normal peritumoral cells, such as cancer-associated fibroblasts in melanoma and keratinocytes in extramammary Paget's disease, which promote tumor progression and predict aggressive behavior and poor prognosis. This review provides an overview of our current understanding of the mechanisms via which podoplanin mediates these pathological skin conditions.

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