Effects and regulation of osteopontin in rat hepatic stellate cells.
Using a cDNA microarray, we identified osteopontin (OPN) as one of the genes upregulated in cultured activated hepatic stellate cells (HSCs). Northern and western blot analyses showed that OPN was increasingly expressed during the progressive activation of cultured rat HSCs, and a significant increase in OPN was observed in carbon tetrachloride-induced rat liver fibrosis. In biliary atresia, OPN protein was predominantly expressed in Kupffer cells and HSCs in the necrotic areas. Incubation of HSCs with recombinant OPN-induced significant proliferative and migratory effects, and induced matrix metalloproteinase 2 production and activation. Moreover, OPN increased type I collagen production and type II transforming growth factor-beta receptor mRNA and protein. In conclusion, this study shows that OPN is expressed in activated HSCs and suggests that the upregulation of OPN might be a central pathway of HSC activation.
Lee
Sung Hee
SH
Medicinal Resources Research Center, College of Pharmacy, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
Seo
Geom Seog
GS
Park
Young Nyun
YN
Yoo
Tae Moo
TM
Sohn
Dong Hwan
DH
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D024042:Collagen Type I / Q000378:metabolism; D006801:Humans; D007728:Kupffer Cells / Q000378:metabolism*; D008099:Liver / Q000166:cytology*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000378:metabolism; D053495:Osteopontin; D051381:Rats; D017207:Rats, Sprague-Dawley; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D012795:Sialoglycoproteins / Q000276:immunology / Q000302:isolation & purification* / Q000502:physiology; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology
D024042:Collagen Type I; D018125:Receptors, Transforming Growth Factor beta; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin; D019716:Tissue Inhibitor of Metalloproteinase-2; D002251:Carbon Tetrachloride; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2