Treatment with antisense oligonucleotide reduces the expression of type I collagen in a human-skin organ-wound model: implications for antifibrotic gene therapy.
Increased collagen expression during wound healing causes scar formation, abnormal contracture, low tensile strength, functional impairment, and disfigurement. A novel ex vivo wound-injury model demonstrated that AS60, an antisense oligonucleotide (ASO) to type I collagen, reduced the mRNA and protein expression of type 1 collagen. Following a cutaneous wound injury in a human-skin organ culture, AS60 injection resulted in a 36% (P < 0.001) and 30% decrease (P < 0.001) in type 1 collagen mRNA and protein expression after 7 days. Similarly, transfection of cultured human fibroblasts with ASO resulted in a 36% decrease (P < 0.001) and a 31% decrease (P < 0.001) in type 1 collagen mRNA and protein expression. Immunofluorescence of human skin organ culture treated with ASO showed a specific reduction in collagen expression. Using AS60 to reduce collagen expression in human skin may have implications for its use as a gene therapy agent to reduce the formation of fibrotic scarring.
Texas Nerve and Paralysis Institute, Houston, TX 77030, USA. nath@drnathmedical.com
Rahul K
RK
Nath
Weijun
W
Xiong
Andrea D
AD
Humphries
Rajinder
R
Beri
D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics*; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D005355:Fibrosis / Q000235:genetics* / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D020320:Oligoribonucleotides, Antisense / Q000494:pharmacology* / Q000627:therapeutic use*; D012871:Skin Diseases / Q000473:pathology / Q000628:therapy*; D014947:Wounds and Injuries / Q000628:therapy*
D024042:Collagen Type I; D020320:Oligoribonucleotides, Antisense