Osteoactivin fragments produced by ectodomain shedding induce MMP-3 expression via ERK pathway in mouse NIH-3T3 fibroblasts.
Intact osteoactivin, a novel type I membrane glycoprotein, were shed at a dibasic motif in the juxtamembrane region in C2C12 myoblasts. Extracellular fragments were secreted into the culture media by a putative metalloprotease. Extracellular fragments of osteoactivin, but not control protein, induced matrix metalloprotease-3 (MMP-3) expression in NIH-3T3 fibroblasts. Epidermal growth factor (ERK) kinase inhibitors inhibited the osteoactivin-mediated MMP-3 expression, whereas the extracellular fragment of osteoactivin activated ERK1/2 and p38 in the mitogen-activated protein kinase pathway. Our results suggest that the extracellular fragments of osteoactivin produced by shedding act as a growth factor to induce MMP-3 expression via the ERK pathway in fibroblasts.
Department of Nutritional Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
Harumi
H
Furochi
Seiko
S
Tamura
Mai
M
Mameoka
Chiharu
C
Yamada
Takayuki
T
Ogawa
Katsuya
K
Hirasaka
Yuushi
Y
Okumura
Takahito
T
Imagawa
Sachiko
S
Oguri
Kazumi
K
Ishidoh
Kyoichi
K
Kishi
Shigeki
S
Higashiyama
Takeshi
T
Nikawa
D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects; D005136:Eye Proteins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis* / Q000235:genetics; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology; D041681:NIH 3T3 Cells; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D005136:Eye Proteins; C445671:Gpnmb protein, mouse; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011480:Protease Inhibitors; D012333:RNA, Messenger; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019278:Matrix Metalloproteinase 3