title: Extra-domain-A fibronectin: a new marker of fibrosis in cutaneous graft-versus-host disease.
abstract: One of the major complications that limit the success of allogeneic stem cell transplantation is graft-versus-host disease (GVHD). The major target organ in GVHD is the skin. Cutaneous GVHD can eventually lead to fibrosis of the skin. Fibronectin mediates a variety of cellular interactions with the extracellular matrix. The molecular and functional diversity of fibronectin (FN) arises from alternative splicing of pre-mRNA. In normal circumstances endothelial cells and fibroblasts synthesize FN without the ED-A domain. In tissue repair and pathologic circumstances such as fibrosis, the ED-A domain is expressed. We hypothesize that expression of ED-A FN is upregulated in patients with cutaneous GVHD. In frozen skin biopsies the expression of ED-A FN was measured at the protein level by immunohistochemistry and at the mRNA level by quantitative real-time PCR (qPCR). In normal control skin, immunohistochemistry showed slight deposits of ED-A FN just under the basal layer. The expression of ED-A FN significantly increased in acute cutaneous GVHD (p<0.05) and ED-A FN was strongly deposited in chronic cutaneous GVHD (p<0.001). Quantitative PCR also showed increased expression of ED-A FN mRNA in acute and chronic cutaneous GVHD compared with normal control skin (p=0.07 and 0.039, respectively). The expression of ED-A FN is increased in the skin of patients with cutaneous GVHD measured both with immunohistochemistry and qPCR. ED-A FN is a new marker of fibrosis in the skin of patients with cutaneous GVHD.
authors.affiliation: Department of Haematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Hanneke M
authors.initials: HM
authors.lastname: van der Straaten
authors.forename: Marijke R
authors.initials: MR
authors.lastname: Canninga-van Dijk
authors.forename: Leo F
authors.initials: LF
authors.lastname: Verdonck
authors.forename: Domenico
authors.initials: D
authors.lastname: Castigliego
authors.forename: H P Eric
authors.initials: HP
authors.lastname: Borst
authors.forename: Jan
authors.initials: J
authors.lastname: Aten
authors.forename: Rob
authors.initials: R
authors.lastname: Fijnheer
mesh_terms: D000328:Adult; D004396:Coloring Agents; D005260:Female; D005353:Fibronectins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005355:Fibrosis; D005819:Genetic Markers; D006086:Graft vs Host Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013194:Staining and Labeling
chemical_list: D004396:Coloring Agents; D005353:Fibronectins; D005819:Genetic Markers; D012333:RNA, Messenger