Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland.
School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
PLoS One. 2019 Jul 23;14(7):e0219938. doi: 10.1371/journal.pone.0219938. eCollection 2019.
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.
Podoplanin (PDPN) 是一种糖蛋白,表达于多种细胞类型,包括角质形成细胞、成纤维细胞和淋巴管内皮细胞。我们发现 PDPN 在小鼠的晚期生长期表达于毛囊 (HF) 角质形成细胞区域和 HF 干细胞区域,但在休止期不表达。重要的是,与对照组小鼠相比,在小鼠的角蛋白细胞特异性 PDPN 缺失 (K5-Cre;PDPNflox/flox) 后,在拔毛诱导的 HF 再生后促进了生长期 HF 的生长。RNA 测序,随后进行基因本体分析,显示从 K5-Cre;PDPNflox/flox 小鼠中分离的 HF 干细胞中的粘着斑和细胞外基质相互作用途径下调。此外,与对照组小鼠相比,从 K5-Cre;PDPNflox/flox 小鼠中分离的 HF 角质形成细胞在细胞黏附测定中与 I 型胶原的相互作用能力降低。综上所述,这些结果表明 PDPN 的缺失促进了 HF 的循环,可能是通过减少粘着斑,同时增强 HF 干细胞向毛囊区域的迁移。它们还表明了针对与脱发相关的疾病的潜在新的治疗策略。