Notch signaling regulates the differentiation of bone marrow-derived cells into smooth muscle-like cells during arterial lesion formation.
Bone marrow- (BM-) derived cells can differentiate into smooth muscle-like cells (SMLC), resulting in vascular pathogenesis. However, the molecular mechanism of the differentiation remains unknown. We have recently reported that Notch signaling promotes while a Notch target HERP1 inhibit the differentiation of mesenchymal cells to SMC. During the differentiation of BM-derived mononuclear cells into smooth muscle alpha-actin (SMA)-positive cells, expression of Jagged1 and SMC-specific Notch3 was increased. Blocking Notch with gamma-secretase inhibitor prevented the induction of SMA. Wire-mediated vascular injury was produced in femoral arteries in mice transplanted with green fluorescent protein (GFP)-positive cells. Many double-positive cells for GFP/Jagged1 or GFP/Notch3 were detected in the thickened neointima. In contrast, only a few SMA-positive cells were positive for GFP in neointima where HERP1, a suppressor for Notch, were abundantly expressed. In conclusion, Notch-HERP1 pathway plays an important role in differentiation of BM-derived mononuclear cells into SMLC.
Doi
Hiroshi
H
Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, Maebashi, Japan.
Iso
Tatsuya
T
Shiba
Yuji
Y
Sato
Hiroko
H
Yamazaki
Miki
M
Oyama
Yoshiaki
Y
Akiyama
Hideo
H
Tanaka
Toru
T
Tomita
Tomoyuki
T
Arai
Masashi
M
Takahashi
Masafumi
M
Ikeda
Uichi
U
Kurabayashi
Masahiko
M
D000818:Animals; D001158:Arteries / Q000293:injuries* / Q000378:metabolism / Q000473:pathology*; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D000072100:Jagged-1 Protein; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D000071656:Receptor, Notch3; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000378:metabolism*; D012097:Repressor Proteins / Q000096:biosynthesis; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D017539:Tunica Intima / Q000293:injuries / Q000378:metabolism / Q000473:pathology
D051792:Basic Helix-Loop-Helix Proteins; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D000071656:Receptor, Notch3; D000074562:Receptor, Notch4; D051880:Receptors, Notch; D012097:Repressor Proteins; D000072099:Serrate-Jagged Proteins; C405693:HEY2 protein, human; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; C499374:NOTCH3 protein, human; C106075:NOTCH4 protein, human