The Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan; International Center of Wound Repair and Regeneration, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Division of Plastic and Reconstructive Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
J Invest Dermatol. 2019 Oct;139(10):2204-2214.e7. doi: 10.1016/j.jid.2019.03.1149. Epub 2019 Apr 12.
Tumor endothelial marker 1 (TEM1), also known as endosialin or CD248, is a type I transmembrane glycoprotein containing a C-type lectin-like domain. It is highly expressed in pericytes and fibroblasts. Dermal fibroblasts play a pivotal role during cutaneous wound healing, especially in the proliferative phase. However, the physiological function of TEM1 in wound healing is still undetermined. During the process of wound healing, the expression of both TEM1 and platelet-derived growth factor (PDGF) receptor α was highly upregulated in myofibroblasts. In vivo, fibroblast activation and collagen deposition in granulation tissues were attenuated, and wound healing was retarded in TEM1-deleted mice. In vitro, the migration, adhesion, and proliferation of NIH3T3 cells were suppressed following TEM1 knockdown by short hairpin RNA. In PDGF-BB-treated NIH3T3 cells, the downstream signal and mitogenic, and chemoattractive effects were inhibited by TEM1 knockdown. In addition, TEM1 and PDGF receptor α were colocalized in subcellular organelles in fibroblasts, and the association of TEM1 and PDGF receptor α was demonstrated by coimmunoprecipitation. In summary, these findings suggested that TEM1, in combination with PDGF receptor α, plays a critical role in wound healing by enhancing the mitogenic and chemoattractive effects of PDGF-BB and collagen deposition in myofibroblasts.
肿瘤内皮标志物 1（TEM1），也称为内皮唾液酸糖蛋白 1 或 CD248，是一种含有 C 型凝集素样结构域的 I 型跨膜糖蛋白。它在周细胞和成纤维细胞中高度表达。真皮成纤维细胞在皮肤创伤愈合过程中起着关键作用，特别是在增殖期。然而，TEM1 在创伤愈合中的生理功能仍未确定。在创伤愈合过程中，肌成纤维细胞中 TEM1 和血小板衍生生长因子（PDGF）受体 α 的表达均被高度上调。在体内，TEM1 缺失小鼠的成纤维细胞活化和肉芽组织中胶原沉积减少，伤口愈合延迟。在体外，短发夹 RNA 敲低 TEM1 可抑制 NIH3T3 细胞的迁移、黏附和增殖。在 PDGF-BB 处理的 NIH3T3 细胞中，TEM1 敲低抑制了下游信号和有丝分裂原以及趋化作用。此外，TEM1 和 PDGF 受体 α 在成纤维细胞的亚细胞细胞器中发生共定位，并且通过共免疫沉淀证明了 TEM1 和 PDGF 受体 α 的关联。总之，这些发现表明，TEM1 与 PDGF 受体 α 结合，通过增强 PDGF-BB 的有丝分裂原和趋化作用以及肌成纤维细胞中胶原的沉积，在创伤愈合中发挥关键作用。
