VLA-5-mediated adhesion to fibronectin accelerates hemin-stimulated erythroid differentiation of K562 cells through induction of VLA-4 expression.
Fibronectin plays important roles in erythropoiesis through the fibronectin receptors VLA-4 and VLA-5. However, the substantial role of these fibronectin receptors and their functional assignment in erythroid differentiation are not yet fully understood. Here, we investigated the effects of cell adhesion to fibronectin on erythroid differentiation using K562 human erythroid progenitor cells. Erythroid differentiation could be induced in K562 cells in suspension by stimulating with hemin. This hemin-stimulated erythroid differentiation was highly accelerated when cells were induced to adhere to fibronectin by treatment with TNIIIA2, a peptide derived from tenascin-C, which has recently been found to induce beta1-integrin activation. Another integrin activator, Mn(2+), also accelerated hemin-stimulated erythroid differentiation. Adhesive interaction with fibronectin via VLA-4 as well as VLA-5 was responsible for acceleration of the hemin-stimulated erythroid differentiation in response to TNIIIA2, although K562 cells should have been lacking in VLA-4. Adhesion to fibronectin forced by TNIIIA2 causally induced VLA-4 expression in K562 cells, and this was blocked by the RGD peptide, an antagonist for VLA-5. The resulting adhesive interaction with fibronectin via VLA-4 strongly enhanced the hemin-stimulated activation of p38 mitogen-activated protein kinase, which was shown to serve as a signaling molecule crucial for erythroid differentiation. Suppression of VLA-4 expression by RNA interference abrogated acceleration of hemin-stimulated erythroid differentiation in response to TNIIIA2. Thus, VLA-4 and VLA-5 may contribute to erythropoiesis at different stages of erythroid differentiation.
Tanaka
Rika
R
Department of Molecular Patho-Physiology, Tokyo University of Science, Noda-Shi, Chiba, Japan.
Owaki
Toshiyuki
T
Kamiya
Sadahiro
S
Matsunaga
Takuya
T
Shimoda
Kazuya
K
Kodama
Hiroaki
H
Hayashi
Ryo
R
Abe
Takashi
T
Harada
Yosei P
YP
Shimonaka
Motoyuki
M
Yajima
Hirofumi
H
Terada
Hiroshi
H
Fukai
Fumio
F
D000595:Amino Acid Sequence; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000378:metabolism; D004920:Erythropoiesis; D005353:Fibronectins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006427:Hemin / Q000378:metabolism*; D006801:Humans; D039041:Integrin alpha4beta1 / Q000235:genetics / Q000378:metabolism*; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D008345:Manganese / Q000494:pharmacology; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D019063:Tenascin / Q000737:chemistry; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D005353:Fibronectins; D039041:Integrin alpha4beta1; D039081:Integrin alpha5beta1; D010455:Peptides; D019063:Tenascin; D008345:Manganese; D006427:Hemin; D048051:p38 Mitogen-Activated Protein Kinases