title: Gene expression in Graves' ophthalmopathy and arm lymphedema: similarities and differences.
abstract: BACKGROUND
  Graves' ophthalmopathy (GO) and lymphedema share some pathogenetic mechanisms, such as edema, inflammation, and adipogenesis. The aim of this study was to examine similarities and differences between chronic GO and chronic lymphedema.
  
  
  METHODS
  Intraorbital adipose tissue was collected from patients with active (n = 10) or chronic GO (n = 10) and thyroid-healthy controls (n = 10). Arm subcutaneous adipose tissue was obtained from patients with chronic arm lymphedema (n = 10), where the unaffected arm served as a control. Gene expression was studied using microarray and real-time polymerase chain reaction.
  
  
  RESULTS
  The following genes were significantly upregulated (p < 0.05) in lymphedema but not in GO and have functions in wound healing, fibrosis, fat metabolism, inflammation, differentiation, development, adhesion, and the cytoskeleton: ATP-binding cassette, sub-family G (WHITE), member 1 (ABCG1), actin, alpha 2, smooth muscle, aorta (ACTA2), secreted frizzled-related protein 2 (SFRP2), tenascin C (TNC), pentraxin-related gene, rapidly induced by IL-1 beta (PTX3), and carboxypeptidase X (M14 family), member 1 (CPMX1). In chronic GO, but not in lymphedema, adipocyte-related immediate early genes known to be overexpressed in patients with active GO were upregulated but at a lower level than previously shown for the active phase. Genes of the Wnt pathway, such as secreted frizzled-related protein 1, 2, and 3, were up- and downregulated in both chronic GO and lymphedema. Parathyroid hormone-like hormone (PTHLH) was downregulated (p = 0.01) and apolipoprotein L domain containing 1 (APOLD1) was upregulated (p = 0.05) in both active and chronic GO.
  
  
  CONCLUSIONS
  There are more differences than similarities between chronic ophthalmopathy and chronic lymphedema, but both conditions exhibit less inflammation and adipogenesis compared to the active phases. In lymphedema, fibrosis dominates. PTHLH, which can inhibit adipogenesis, is downregulated both in active and chronic ophthalmopathy, indicating the possibility of an increased risk of adipogenesis.
authors.affiliation: Department of Endocrinology, Skåne University Hospital, CRC, Malmö, Sweden. tereza.planck@med.lu.se
authors.forename: Tereza
authors.initials: T
authors.lastname: Planck
authors.forename: Hemang
authors.initials: H
authors.lastname: Parikh
authors.forename: Håkan
authors.initials: H
authors.lastname: Brorson
authors.forename: Tuve
authors.initials: T
authors.lastname: Mårtensson
authors.forename: Peter
authors.initials: P
authors.lastname: Åsman
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.forename: Bengt
authors.initials: B
authors.lastname: Hallengren
authors.forename: Mikael
authors.initials: M
authors.lastname: Lantz
mesh_terms: D050156:Adipogenesis / Q000502:physiology*; D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D001132:Arm / Q000473:pathology; D001943:Breast Neoplasms / Q000150:complications; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D049970:Graves Ophthalmopathy / Q000378:metabolism*; D006801:Humans; D008209:Lymphedema / Q000209:etiology / Q000378:metabolism*; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D044162:Parathyroid Hormone-Related Protein / Q000096:biosynthesis; D015854:Up-Regulation
chemical_list: C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein