Effect of prolyl 4-hydroxylase inhibitor on fibroblast collagen production in vitro: an approach to the treatment of systemic sclerosis.
Prolyl 4-hydroxylase (PH), which catalyzes the conversion of prolyl residues to 4-hydroxyproline, plays a central role in the synthesis and secretion of collagen. We demonstrated that fibroblasts from patients with systemic sclerosis produced significantly more PH than those from healthy subjects. To regulate excessive collagen production by scleroderma fibroblasts, we examined the effect of a PH inhibitor on collagen production by scleroderma fibroblasts. Fibrostatin-C, a PH inhibitor, significantly decreased the amount of procollagen (type I) production by scleroderma fibroblasts (p < 0.01). We suggest that this PH inhibitor might be a valid antifibrotic agent useful for the treatment of patients with scleroderma.
Kawaguchi
Y
Y
First Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Harigai
M
M
Kitani
A
A
Suzuki
K
K
Kawakami
M
M
Ishizuka
T
T
Hidaka
T
T
Hara
M
M
Kawagoe
M
M
Nakamura
H
H
D015152:Blotting, Northern; D003094:Collagen / Q000378:metabolism*; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology*; D011347:Procollagen / Q000378:metabolism; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000188:drug therapy / Q000378:metabolism*
D005353:Fibronectins; D009285:Naphthoquinones; D011347:Procollagen; D012333:RNA, Messenger; D003094:Collagen; C058033:fibrostatin C; D011393:Procollagen-Proline Dioxygenase; D003545:Cysteine; D006909:Hydroxyproline