Osteopontin is a myosphere-derived secretory molecule that promotes angiogenic progenitor cell proliferation through the phosphoinositide 3-kinase/Akt pathway.
We have reported that skeletal myosphere-derived progenitor cells (MDPCs) can differentiate into vascular cells, and that MDPC transplantation into cardiomyopathic hearts improves cardiac function. However, the autocrine/paracrine molecules and underlying mechanisms responsible for MDPC growth have not yet been determined. To explore the molecules enhancing the proliferation of MDPCs, we performed serial analysis of gene expression and signal sequence trap methods using RNA isolated from MDPCs. We identified osteopontin (OPN), a secretory molecule, as one of most abundant molecules expressed in MDPCs. OPN provided a proliferative effect for MDPCs. MDPCs treated with OPN showed Akt activation, and inhibition of the phosphoinositide 3-kinase (PI3K)/Akt pathway repressed the proliferative effect of OPN. Furthermore, OPN-pretreated MDPCs maintained their differentiation potential into endothelial and vascular smooth muscle cells. These findings indicate an important role of OPN as an autocrine/paracrine molecule in regulating the proliferative growth of muscle-derived angiogenic progenitor cells via the PI3K/Akt pathway.
Ogata
Takehiro
T
Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto, Japan.
Ueyama
Tomomi
T
Nomura
Tetsuya
T
Asada
Satoshi
S
Tagawa
Masashi
M
Nakamura
Tomoyuki
T
Takahashi
Tomosaburo
T
Matsubara
Hiroaki
H
Oh
Hidemasa
H
D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D004305:Dose-Response Relationship, Drug; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D018482:Muscle, Skeletal / Q000378:metabolism; D018919:Neovascularization, Physiologic; D053495:Osteopontin / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012313:RNA / Q000378:metabolism
D005353:Fibronectins; D053495:Osteopontin; D012313:RNA; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt