An important role of podoplanin in hair follicle growth.

Sun-Young Yoon,Lothar C Dieterich,Yuliang He,Michael Detmar,Ohsang Kwon,Lorenz Brunner,Marko Sesartic,Carlotta Tacconi

doi:10.1371/journal.pone.0219938

Sun-Young Yoon, Lothar C Dieterich + Show 6 more

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https://doi.org/10.1371/journal.pone.0219938

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Abstract

Podoplanin (PDPN) is a glycoprotein that is expressed by various cell types, including keratinocytes, fibroblasts, and lymphatic endothelial cells. We found that PDPN is expressed in the hair follicle (HF) keratinocyte region and HF stem cell area during the late anagen phase but not during the telogen phase in mice. Importantly, keratinocyte-specific PDPN deletion in mice (K5-Cre;PDPNflox/flox) promoted anagen HF growth after depilation-induced HF regeneration as compared to control mice. RNA sequencing, followed by gene ontology analysis, showed down-regulation of focal adhesion and extracellular matrix interaction pathways in HF stem cells isolated from K5-Cre;PDPNflox/flox mice as compared to control mice. Furthermore, HF keratinocytes isolated from K5-Cre;PDPNflox/flox mice exhibited a decreased ability to interact with collagen type I in cell adhesion assays. Taken together, these results show that PDPN deletion promotes HF cycling, possibly via reduced focal adhesion and concomitantly enhanced migration of HF stem cells towards the bulb region. They also indicate potential new therapeutic strategies for the treatment of conditions associated with hair loss.

Highlights

Podoplanin (PDPN) is a 38-kDa mucin-type transmembrane glycoprotein consisting of a heavily glycosylated extracellular domain, a single transmembrane domain, and a short, nine amino acid cytoplasmic tail [1, 2]
These results indicate that PDPN is expressed in hair follicle (HF), in the HF keratinocyte region and HF stem cell area
These results indicate that PDPN is expressed in HF keratinocytes and HF stem cells during the late-anagen growth phase but not during the telogen phase, suggesting that PDPN might be involved in HF cycling

Summary

Introduction

Podoplanin (PDPN) is a 38-kDa mucin-type transmembrane glycoprotein consisting of a heavily glycosylated extracellular domain, a single transmembrane domain, and a short, nine amino acid cytoplasmic tail [1, 2]. Expression of PDPN is upregulated in various tumor types, including squamous cell carcinoma, angiosarcoma, hemangioblastoma, malignant mesothelioma, and brain tumors [3,4,5], and correlates with increased tumor cell motility and metastasis [6]. Not detected in the normal interfollicular epidermis, PDPN is expressed in epidermal keratinocytes during wound healing, in psoriasis and during mouse skin carcinogenesis [11,12,13]. PDPN is expressed in the basal cell layer of the sebaceous gland and the outer root sheath cells of hair follicle (HF).

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