title: Synthesis of collagen I in collagenous sprue.
abstract: OBJECTIVE
  Collagenous sprue (CS) is a rare severe malabsorption syndrome of unknown etiology, characterized by villus atrophy and a broad subepithelial collagen band. We studied the expression patterns of genes involved in fibrogenesis and fibrolysis and analyzed the composition of the subepithelial collagen band in CS compared with untreated celiac diseases (CDs).
  
  
  METHODS
  Duodenal biopsies from 2 patients with CS were hybridized with (35)S-labeled RNA probes for procollagen alpha1(I), matrix metalloproteinases (MMPs)-1 and -3, and tissue inhibitor of MMP-1 (TIMP-1). Numbers of positive subepithelial and lamina propria cells and grain density per cell were determined microscopically. Immunohistochemistry for collagens I, III, IV, XIV, and tenascin was performed by the immunoalkaline phosphatase method. Findings were compared with earlier data from patients with untreated CD.
  
  
  RESULTS
  Numbers of cells expressing procollagen I, MMP-1, and MMP-3 mRNA were similar, but subepithelial procollagen I transcripts per cell were significantly increased (42 and 38 vs 18 [13-23]; P < .05) in CS compared with CD, whereas cellular transcript densities for MMP-1 and MMP-3 mRNA were similar. In addition, the number of TIMP-1 mRNA-positive cells was higher in CS compared with CD (32 and 25 vs 16.5 [4-25]; P < .05). The subepithelial collagenous bands stained for collagen I, collagen III, and tenascin.
  
  
  CONCLUSIONS
  The prominent subepithelial matrix deposition in CS is due to increased expression of the main fibrogenic genes (procollagen I and TIMP-1) by myofibroblastic cells, whereas expression of fibrolytic MMPs remains unaltered.
authors.affiliation: Department of Medicine I, Gastroenterology, Infectious Diseases and Rheumatology, Universitätsmedizin Berlin, Berlin, Germany. severin.daum@charite.de
authors.forename: Severin
authors.initials: S
authors.lastname: Daum
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Foss
authors.forename: Detlef
authors.initials: D
authors.lastname: Schuppan
authors.forename: Ernst-Otto
authors.initials: EO
authors.lastname: Riecken
authors.forename: Martin
authors.initials: M
authors.lastname: Zeitz
authors.forename: Reiner
authors.initials: R
authors.lastname: Ullrich
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics*; D004386:Duodenum / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008286:Malabsorption Syndromes / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1