Antisense oligonucleotide against 47-kDa heat shock protein (Hsp47) inhibits wound-induced enhancement of collagen production.
It is well known that excessive collagen synthesis during the wound-healing process causes scar formation. Our recent in-vivo study indicates that antisense treatment against 47-kDa heat shock protein (Hsp47), a collagen-specific molecular chaperone, relieves scar formation following skin wounds in rats [Wang et al., Plast. Reconstr. Surg., in press]. In order to understand the mechanism of this phenomenon, we examined the effects of antisense treatment on the expression of mRNAs and proteins of Hsp47 and collagens in fibroblasts derived from wounded rat tongues. Hsp47 and procollagen alpha1(I) and alpha1(III) mRNAs were consistently increased after wounding and were maximal at day 5 post-injury. Treatment with antisense oligonucleotide against Hsp47 efficiently blocked the production of procollagen alpha2(I) and alpha1(III) proteins, but had little effect on their mRNA levels. Therefore, we conclude that antisense oligonucleotide against Hsp47 inhibits the production of procollagen type I and III proteins in fibroblasts derived from wounded tongues, overcoming the increase in their mRNAs.
Ohba
S
S
Division of Oral and Maxillofacial Surgical Reconstruction and Functional Restoration, Department of Developmental and Reconstructive Medicine, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto, Japan. d499004b@stcc.nagasaki-u.ac.jp
Wang
Z L
ZL
Baba
T T
TT
Nemoto
T K
TK
Inokuchi
T
T
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics; D024061:Collagen Type III / Q000096:biosynthesis / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D011347:Procollagen / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014059:Tongue / Q000293:injuries / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
D024042:Collagen Type I; D024061:Collagen Type III; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D016376:Oligonucleotides, Antisense; D011347:Procollagen; D012333:RNA, Messenger; C494662:Serpinh1 protein, rat