title: A Comparison of Gene Expression of Decorin and MMP13 in Hypertrophic Scars Treated With Calcium Channel Blocker, Steroid, and Interferon: A Human-Scar-Carrying Animal Model Study.
abstract: BACKGROUND
  The formation of hypertrophic scaring (HSc) is an abnormal wound-healing response. In a previous study, an animal model with human scar tissue implanted into nude mice (BALB/c) has been successfully established. The effects of verapamil as well as combination therapy with verapamil and kenacort have been studied and compared.
  
  
  OBJECTIVE
  To treat persistent hypertrophic scars, local injection of drugs composed of steroids, calcium channel blockers (CCBs), and interferon might be a good method. What is the best dose of the regimen and what are the mechanisms are also a worthwhile study.
  
  
  METHODS
  Scar specimens were harvested from patients with HSc or Keloid resulting from burn injury, and then implanted to BALB/c-nu nude mice for 4 weeks. Before implantation, the specimen was either injected with or without drugs such as steroids (kenacort), CCBs (verapamil), and interferons (INFα2b), respectively. After the removal of implants, quantitative gene expressions of decorin and collagenase (MMP13) were measured using a real-time polymerase chain reaction to detect their mRNAs. Two way-ANOVA and Post Hoc were used for statistical analysis using the software SPSS 15.0.
  
  
  RESULTS
  All drug-treated groups increased the expressions of decorin and MMP13 in comparison with those in noninjected group (p < .001) in a dose-dependent manner. Comparing equal amounts of individual drugs, gene expression of decorin was increased with increasing injection amount, and the best result in low amount of injection (0.02 mL of each) was shown in the group injected with INFα2b followed by kenacort and verapamil. However, the results were changed while injection amount was up to 0.04 mL and the strongest decorin gene expression was found in kenacort injection. Regarding MMP-13 expression, low-amount injection (0.02 mL) of INFα2b has strongest gene expression followed by kenacort and verapamil, but in the large-amount regimes (0.04 mL), verapamil had strongest gene expression followed by INFα2b and kenacort.
  
  
  CONCLUSIONS
  This study showed that the kenacort, verapamil, and INFα2b all inhibited HSc in a dose-dependent manner through the evidence of gene expression of decorin and MMP13. In comparison with the injections between small amounts of drugs, INFα2b potentiated the strongest decorin and MMP13 expression. On the contrary, among the large-amount injection regimes, kenacrot was more effective on decorin expression as verapamil to MMP13 expression. To decrease side effects from the drugs and produce promising results for the clinical practice, it is suggested to maintain the dose of INFα2b along with an increased dose of verapamil for HSc improvement.
authors.affiliation: Department of Plastic Surgery, Linkou Burn Center, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan.
authors.forename: Shih-Yi
authors.initials: SY
authors.lastname: Yang
authors.forename: Jui-Yung
authors.initials: JY
authors.lastname: Yang
authors.forename: Yen-Chang
authors.initials: YC
authors.lastname: Hsiao
authors.forename: Shiow-Shuh
authors.initials: SS
authors.lastname: Chuang
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002056:Burns / Q000150:complications; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D002921:Cicatrix / Q000188:drug therapy* / Q000235:genetics; D017439:Cicatrix, Hypertrophic / Q000188:drug therapy / Q000235:genetics; D058575:Decorin / Q000235:genetics*; D003879:Dermatologic Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D007271:Injections, Intradermal; D015552:Injections, Intralesional; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D007627:Keloid / Q000188:drug therapy / Q000235:genetics; D053509:Matrix Metalloproteinase 13 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014222:Triamcinolone Acetonide / Q000008:administration & dosage; D014700:Verapamil / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D002121:Calcium Channel Blockers; D058575:Decorin; D003879:Dermatologic Agents; D005938:Glucocorticoids; D000077190:Interferon alpha-2; D016898:Interferon-alpha; C000614170:Interferon-alpha2b; D014700:Verapamil; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D014222:Triamcinolone Acetonide