title: Mast cell tryptase stimulates production of decorin by human testicular peritubular cells: possible role of decorin in male infertility by interfering with growth factor signaling.
abstract: BACKGROUND
  Myofibroblastic, peritubular cells in the walls of seminiferous tubules produce low levels of the extracellular matrix (ECM) protein decorin (DCN), which has the ability to interfere with growth factor (GF) signaling. In men with impaired spermatogenesis, fibrotic remodeling of these walls and accumulation of tryptase-positive mast cells (MCs) occur.
  
  
  METHODS
  Human testicular biopsies with normal and focally impaired spermatogenesis (mixed atrophy) were subjected to immunohistochemistry and laser micro-dissection followed by RT-PCR. Primary human testicular peritubular cells (HTPCs), which originate from normal and fibrotically altered testes (HTPC-Fs), were studied by qRT-PCR, western blotting, enzyme-linked immunosorbent assay measurements and Ca(2+) imaging. Phosphorylation and viability/proliferation assays were performed.
  
  
  RESULTS
  Immunohistochemistry revealed DCN deposits in the walls of tubules with impaired spermatogenesis. Mirroring the situation in vivo, HTPC-Fs secreted more DCN than HTPCs (P < 0.05). In contrast to HTPCs, HTPC-Fs also responded to the main MC product, tryptase, and to a tryptase receptor (PAR-2) agonist by further increased production of DCN (P < 0.05). Several GF receptors (GFRs) are expressed by HTPCs and HTPC-Fs. DCN acutely increased intracellular Ca(2+)-levels and phosphorylated epidermal GF (EGFR) within minutes. Platelet-derived GF (PDGF) and EGF induced strong mitogenic responses in HTPC/-Fs, actions that were blocked by DCN, suggesting that DCN in the ECM interferes with GF/GFRs signaling of peritubular cells of the human testis.
  
  
  CONCLUSIONS
  The data indicate that the increase in testicular DCN found in male infertility is a consequence of actions of MC-derived tryptase. We propose that the increases in DCN may consequently imbalance the paracrine signaling pathways in human testis.
authors.affiliation: Anatomy and Cell Biology, Center for Integrated Protein Science Munich, Ludwig-Maximilians-University Munich, D-80802 Munich, Germany. mayerhofer@lrz.uni-muenchen.de
authors.forename: M
authors.initials: M
authors.lastname: Adam
authors.forename: J U
authors.initials: JU
authors.lastname: Schwarzer
authors.forename: F M
authors.initials: FM
authors.lastname: Köhn
authors.forename: L
authors.initials: L
authors.lastname: Strauss
authors.forename: M
authors.initials: M
authors.lastname: Poutanen
authors.forename: A
authors.initials: A
authors.lastname: Mayerhofer
mesh_terms: D001706:Biopsy / Q000379:methods; D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D058575:Decorin / Q000096:biosynthesis*; D005355:Fibrosis / Q000473:pathology; D006801:Humans; D007248:Infertility, Male / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000166:cytology; D010766:Phosphorylation; D015398:Signal Transduction; D013091:Spermatogenesis; D013737:Testis / Q000378:metabolism* / Q000473:pathology; D053802:Tryptases / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*
chemical_list: D058575:Decorin; D036341:Intercellular Signaling Peptides and Proteins; D053802:Tryptases; D002118:Calcium