Exogenous nitric oxide enhances the synthesis of type I collagen and heat shock protein 47 by normal human dermal fibroblasts.
BACKGROUND
It is well established that the alterations of dermal matrix contributes to skin aging characterized by wrinkles. On the other hand, physiological NO is useful to maintain skin homeostasis such as a vasodilatation. However, a role of NO on production of dermal matrix has been clarified.


OBJECTIVE
In this study, we have attempted to analyze the role of NO on type I collagen synthesis of normal human dermal fibroblasts including expression of procollagen alphaI S(1) mRNA/protein and heat shock protein 47 (HSP47).


METHODS
The effects of NO which was generated by two types of NO donors, sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP), on type I collagen and HSP47 and their related mRNA expression were examined with ELISA and RT-PCR.


RESULTS
NO was significantly accelerated the production of type I collagen by fibroblasts corresponding with up-regulation of procollagen alphaI (1) mRNA. Furthermore, NO increased both levels of HSP47 protein and mRNA in fibroblasts in a dose-dependent manner.


CONCLUSIONS
These results suggest that NO has dual effects on collagen synthesis by fibroblasts as follows; one is the direct stimulation of collagen synthesis due to the up-regulation of procollagen alphaI(1) mRNA, and the other is an indirect effect through the increase of HSP47 mRNA expression. This is the first report that exogenous NO stimulates HSP47 production by dermal fibroblasts.
Obayashi
Kei
K
Cosmos Technical Center Co. Ltd., 3-24-3 Hasune, Itabashi-Ku, Tokyo 174-0046, Japan.
Akamatsu
Hirohiko
H
Okano
Yuri
Y
Matsunaga
Kayoko
K
Masaki
Hitoshi
H
D002478:Cells, Cultured; D024042:Collagen Type I / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D020405:Dermis / Q000166:cytology* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D050958:HSP47 Heat-Shock Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011347:Procollagen / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D024042:Collagen Type I; D050958:HSP47 Heat-Shock Proteins; D020030:Nitric Oxide Donors; D011347:Procollagen; D012333:RNA, Messenger; C110881:S-nitro-N-acetylpenicillamine; D009599:Nitroprusside; D009569:Nitric Oxide; D010396:Penicillamine