Stimulation of collagen expression and glycosaminoglycan synthesis by midkine in human skin fibroblasts.
Midkine is a retinoid-inducible regulator of cell differentiation and cell growth in developing embryonic tissues. The effects of midkine on the expression of the extracellular matrix components, collagens and glycosaminoglycans, in dermal fibroblasts were studied. Midkine did not alter fibroblast proliferation. Collagen synthesis was stimulated in a dose- and exposure time-dependent manner and the maximum two-fold stimulation was achieved at a concentration of 100 ng/ml for 72 h treatment. Midkine increased the synthesis of type I and III collagens to the same extent. Glycosaminoglycan synthesis was also stimulated two-fold, mainly accounted for by an increase in hyaluronan synthesis. Midkine enhanced mRNA levels of alpha 1 (I), alpha 1 (III), alpha 1 (VI) collagens, transforming growth factor beta 1 and matrix metalloprotease-2 but did not alter the mRNA levels of elastin, MMP-1 and tissue inhibitor of metalloproteases-1. These results suggest that midkine is a potent stimulator of collagen and glycosaminoglycan synthesis and may prove useful in the therapy of delayed wound healing.
Yamada
H
H
Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
Inazumi
T
T
Tajima
S
S
Muramatsu
H
H
Muramatsu
T
T
D002352:Carrier Proteins / Q000494:pharmacology*; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics; D016207:Cytokines; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006025:Glycosaminoglycans / Q000096:biosynthesis*; D006801:Humans; D000078792:Midkine; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000187:drug effects / Q000378:metabolism
D002352:Carrier Proteins; D016207:Cytokines; D006025:Glycosaminoglycans; D012333:RNA, Messenger; D000078792:Midkine; D003094:Collagen