title: Hyalurosome gene regulation and dose-dependent restoration of skin atrophy by retinaldehyde and defined-size hyaluronate fragments in dermatoporosis.
abstract: BACKGROUND
  Dermatoporosis is an emerging clinical condition caused by chronological skin aging, long-term sun exposure and chronic use of corticosteroids; however, genomic expression in dermatoporosis and the efficacy of different therapeutic approaches to prevent and treat dermatoporosis have not been investigated so far.
  
  
  OBJECTIVE
  We examined the possible effect of topical retinaldehyde (RAL) and defined-size hyaluronate fragments (HAFi) on the expression of hyalurosome genes potentially involved in the pathogenesis of dermatoporosis. We also explored the effect of different concentrations of HAFi on skin thickness.
  
  
  METHODS
  13 persons were separated into a young control group (n = 8) and a dermatoporosis group (n = 5). Topical treatment of both groups with a combination of 0.05% RAL and 1 or 0.2% HAFi was applied on the forearm twice daily for 30 days. Forearm skin biopsies of both groups were performed before and after application. Hyalurosome genes CD44, heparin-binding epidermal growth factor (HB-EGF), ErbB1, hyaluronate synthase 3 (HAS3) and Hyal2 were chosen as potential markers of dermatoporosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed for quantification of mRNA expression of the target hyalurosome genes. Measurement of forearm skin thickness before and after treatment was performed by ultrasonography. Analysis of the results was done by Student's t test. A p value <0.05 was considered statistically significant.
  
  
  RESULTS
  In qRT-PCR analysis the relative expression of hyalurosome (CD44, HAS3, HB-EGF) genes was found to be reduced in patients prior to topical treatment and to be notably increased following treatment. The reduced expression of CD44 and HAS3 in patients was specifically restored in dermatoporotic patients after treatment. No difference in skin thickness was observed in controls after treatment. The treatment caused a significant increase in skin thickness in dermatoporotic patients. This increase was more significant with 1% HAFi when compared to 0.2% HAFi. RAL and HAFi also caused a significant reduction in purpuric lesions in patients with dermatoporosis.
  
  
  CONCLUSIONS
  Our results indicate that topically applied RAL and HAFi regulate hyalurosome gene expression in dermatoporosis and that they show a dose-dependent effect on the correction of skin atrophy in dermatoporotic patients.
authors.affiliation: Department of Dermatology, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: Damjan S
authors.initials: DS
authors.lastname: Nikolic
authors.forename: Charis
authors.initials: C
authors.lastname: Ziori
authors.forename: Maria
authors.initials: M
authors.lastname: Kostaki
authors.forename: Lionel
authors.initials: L
authors.lastname: Fontao
authors.forename: Jean-Hilaire
authors.initials: JH
authors.lastname: Saurat
authors.forename: Gürkan
authors.initials: G
authors.lastname: Kaya
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000287:Administration, Topical; D001284:Atrophy / Q000000981:diagnostic imaging / Q000473:pathology; D001706:Biopsy; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D005542:Forearm; D005786:Gene Expression Regulation; D066257:Heparin-binding EGF-like Growth Factor / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000235:genetics*; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D006821:Hyaluronoglucosaminidase / Q000096:biosynthesis / Q000235:genetics*; D015603:Keratinocytes / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012172:Retinaldehyde / Q000008:administration & dosage*; D012189:Retrospective Studies; D012867:Skin / Q000000981:diagnostic imaging / Q000473:pathology; D012871:Skin Diseases / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014463:Ultrasonography
chemical_list: D000276:Adjuvants, Immunologic; D015815:Cell Adhesion Molecules; D066257:Heparin-binding EGF-like Growth Factor; D018960:Hyaluronan Receptors; D012333:RNA, Messenger; D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase; C066852:hyaluronidase PH-20; D012172:Retinaldehyde