Effects of decorin on the expression of alpha-smooth muscle actin in a human myofibroblast cell line.
Myofibroblasts are metabolically and morphologically distinctive fibroblasts expressing alpha-smooth muscle actin (alpha-SMA), and their activation plays a key role in development of the fibrotic response. In an activated state, myofibroblasts cease to proliferate and start to synthesize large amounts of extracellular component proteins. The expression of alpha-SMA correlates with the activation of myofibroblasts. Decorin, a member of the small leucine-rich proteoglycan gene family, has been implicated in the negative control of cell proliferation primarily by upregulating the expression of p21, a potent inhibitor of cyclin-dependent kinase. In order to examine the effect of decorin on myofibroblast cell growth, we rendered a human lung myofibroblast cell line, MRC-5, quiescent by either cell-cell contact or serum starvation, and examined the relationship between decorin and alpha-SMA expression in these cells. The expression of decorin in cells made quiescent by serum starvation was lower than that in cells made quiescent by cell-cell contact. In contrast, the expression of alpha-SMA in cells made quiescent by cell-cell contact was lower than that in cells made quiescent by serum starvation. Furthermore, forced expression of decorin was accompanied by a suppression of alpha-SMA expression, whereas knocking down of decorin expression by RNA interference increased the expression of alpha-SMA.
Nakatani
Tatsuya
T
Department of Biochemistry, Kinki University School of Medicine, 377-2, Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan.
Honda
Eiko
E
Hayakawa
Sumio
S
Sato
Mayumi
M
Satoh
Ken
K
Kudo
Masatoshi
M
Munakata
Hiroshi
H
D000199:Actins / Q000378:metabolism*; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D009130:Muscle, Smooth / Q000378:metabolism*; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014746:Vimentin / Q000378:metabolism
D000199:Actins; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D014746:Vimentin