title: SFRP2 and slug contribute to cellular resistance to apoptosis in hypertrophic scars.
abstract: Hypertrophic scars (HS) are skin disorders which occur after wounding and thermal injury. Our previous studies have suggested that secreted frizzled-related protein 2 (SFRP2) is involved in HS formation and that the suppression of SFRP2 promotes apoptosis of hypertrophic scar fibroblasts (HSFBs). However, the mechanisms have not been clarified. Previous studies revealed that Slug expression inhibits cell apoptosis, in vitro and in vivo, and SFRP2 regulates the expression of Slug in cervical cancer cells. In the present study, we quantified differential expression levels of expression of SFRP2 and Slug in HS and normal skin tissues by immunohistochemistry, both of which have important anti-apoptosis roles. Furthermore, a short hairpin RNA approach was adopted to investigate the potential function of SFRP2 and Slug in HSFB apoptosis. Cell apoptosis was detected using fluorescence-activated cell sorting and Caspase-3 activity was assayed by spectrophotometry. This study demonstrates that SFRP2 expression, as well as Slug, is dramatically up-regulated in HS relative to normal skin tissues, and the Slug expression is positively correlated with SFRP2. Slug expression was down-regulated in SFRP2-deficient cells, and the down-regulation of Slug expression increased sensitivity to apoptosis which was induced through a caspase-3-dependent pathway. The infected cells with reduced levels of Slug were tested for the expression of apoptosis-related genes (Bcl-2, Bax and PUMA) which were previously identified as Slug targets. Bcl-2 expression was down-regulated in Slug-deficient cells. In conclusion, SFRP2 appears to interact with Slug to affect the apoptosis of hypertrophic scar fibroblasts.
authors.affiliation: Department of Plastic Surgery, Southwest Hospital, Third Military Medical University, Chongqing, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.forename: Zhenxiang
authors.initials: Z
authors.lastname: Wang
authors.forename: Shirong
authors.initials: S
authors.lastname: Li
authors.forename: Guangjian
authors.initials: G
authors.lastname: Zhao
authors.forename: Maosheng
authors.initials: M
authors.lastname: Tian
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Sun
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D017439:Cicatrix, Hypertrophic / Q000503:physiopathology*; D017931:DNA Primers; D005434:Flow Cytometry; D020868:Gene Silencing; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D017931:DNA Primers; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C109618:SFRP2 protein, human; D000094742:Secreted Frizzled-Related Proteins; C000604407:SNAI1 protein, human