title: Characterization of hyaluronan and TSG-6 in skin scarring: differential distribution in keloid scars, normal scars and unscarred skin.
abstract: BACKGROUND
  Hyaluronan (HA) is a major component of the extracellular matrix (ECM) with increased synthesis during tissue repair. Tumour necrosis factor-stimulated gene-6 (TSG-6) is known to catalyze the covalent transfer of heavy chains (HC1 and HC2) from inter-α-inhibitor (IαI) onto HA, and resultant HC•HA complexes have been implicated in physiological and pathological processes related to remodelling and inflammation.
  
  
  OBJECTIVE
  The aims of this study were to determine the expression of HA, TSG-6 and the IαI polypeptides in unscarred skin, normal scars and keloid scars.
  
  
  METHODS
  Formalin-fixed paraffin-embedded sections of unscarred skin, normal scars and keloid scars were prepared from patient samples collected during scar revision surgery. Haematoxylin and eosin, as well as immunofluorescent staining for HA, TSG-6 and the three polypeptide chains of IαI (i.e. HC1, HC2 and bikunin) were performed.
  
  
  RESULTS
  All skin types stained positive for TSG-6, HC1, HC2 and bikunin, associated with keratinocytes, fibroblasts and skin appendages all in close proximity to HA. Keloid lesions showed altered HA organization patterns compared with unscarred skin and normal scars. TSG-6 staining was significantly more intense in the epidermis compared with the dermis of all sample types. There was a significant reduction in TSG-6 levels within keloid lesions compared with the dermis of unscarred skin (P=0.017).
  
  
  CONCLUSIONS
  TSG-6 is expressed in unscarred skin, where its close association with HA and IαI could give rise to TSG-6-mediated HC•HA formation within this tissue. A reduction in the beneficial effects of TSG-6, caused by diminished protein levels in keloid lesions, could contribute to this abnormal scarring process.
authors.affiliation: Department of Plastic & Reconstructive Surgery, University Hospital of South Manchester NHS Foundation Trust, and Plastic & Reconstructive Surgery Research, Manchester Interdisciplinary Biocentre, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: K T
authors.initials: KT
authors.lastname: Tan
authors.forename: D A
authors.initials: DA
authors.lastname: McGrouther
authors.forename: A J
authors.initials: AJ
authors.lastname: Day
authors.forename: C M
authors.initials: CM
authors.lastname: Milner
authors.forename: A
authors.initials: A
authors.lastname: Bayat
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000510:Alpha-Globulins / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002921:Cicatrix / Q000378:metabolism* / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism*; D007627:Keloid / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D000510:Alpha-Globulins; D015815:Cell Adhesion Molecules; C072273:TNFAIP6 protein, human; C011877:inter-alpha-inhibitor; D006820:Hyaluronic Acid