Fibulin-5 accelerates elastic fibre assembly in human skin fibroblasts.
Fibulin-5 null mice display abnormalities in the elastic fibres in the dermis. We postulated, therefore, that fibulin-5 might be a regulator of elastic fibre assembly and stability. To clarify the role of fibulin-5 in elastic fibre formation, we employed in vitro systems that allowed increasing expression of elastic fibre components by gene transduction using retroviral vector constructs. First, the human tropoelastin gene (ELN) was transduced into human dermal fibroblasts, which resulted in elevated gene expression. These cells were then cultured in monolayer, but the overexpression of ELN in this system did not alter the assembly of elastic fibres. However, incubation of fibroblasts with TGF-beta1 resulted in elastic fibre accumulation, and the expression of fibulin-5 was enhanced by TGF-beta1. Thus, we overexpressed human fibulin-5 cDNA in dermal fibroblasts using a retroviral vector containing a cytomegalovirus (CMV) promoter. These cells deposited elastic fibres. These results suggest that fibulin-5 is a critical component in the control of elastic fibre assembly by dermal fibroblasts.
Katsuta
Yuji
Y
Shiseido Life Science Research Center, Kanazawa-ku, Yokohama, Japan. yuji.katsuta@to.shiseido.co.jp
Ogura
Yuki
Y
Iriyama
Shunsuke
S
Goetinck
Paul F
PF
Klement
John F
JF
Uitto
Jouni
J
Amano
Satoshi
S
D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology* / Q000502:physiology; D004547:Elastic Tissue / Q000378:metabolism*; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D012333:RNA, Messenger / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D014161:Transduction, Genetic; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
D016326:Extracellular Matrix Proteins; C492373:FBLN5 protein, human; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D004549:Elastin