Tumor Endothelial Marker 1 (TEM1/Endosialin/CD248) Enhances Wound Healing by Interacting with Platelet-Derived Growth Factor Receptors
Journal
Journal of Investigative Dermatology
Journal Volume
139
Journal Issue
10
Pages
2204_2214.e7
Date Issued
2019
Author(s)
Hong Y.-K.
Lee Y.-C.
Cheng T.-L.
Lai C.-H.
Hsu C.-K.
Kuo C.-H.
Hsu Y.-Y.
Li J.-T.
Chang B.-I.
Ma C.-Y.
Wang K.-C.
Shi G.-Y.
Wu H.-L.
Abstract
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. ? 2019 The Authors
SDGs
Other Subjects
alpha smooth muscle actin; collagen; endosialin; messenger RNA; platelet derived growth factor alpha receptor; platelet derived growth factor BB; platelet derived growth factor receptor; short hairpin RNA; leukocyte antigen; platelet derived growth factor receptor; tumor endothelial marker 1, mouse; tumor protein; adult; animal cell; animal experiment; animal model; animal tissue; Article; cell activation; cell adhesion; cell migration; cell organelle; cell proliferation; comparative study; confocal microscopy; controlled study; fibroblast; gene expression; gene knockdown; gene silencing; in vitro study; in vivo study; male; mitogenicity; mouse; myofibroblast; nonhuman; priority journal; protein interaction; skin injury; upregulation; wound healing; animal; disease model; gene expression regulation; genetics; human; injury; metabolism; pathology; physiology; procedures; randomization; real time polymerase chain reaction; time factor; transgenic mouse; treatment outcome; Western blotting; wound healing; Animals; Antigens, CD; Blotting, Western; Disease Models, Animal; Gene Expression Regulation; Humans; Mice; Mice, Transgenic; Neoplasm Proteins; Random Allocation; Real-Time Polymerase Chain Reaction; Receptors, Platelet-Derived Growth Factor; Time Factors; Treatment Outcome; Up-Regulation; Wound Healing; Wounds and Injuries
Type
journal article