title: Lateral growth limitation of corneal fibrils and their lamellar stacking depend on covalent collagen cross-linking by transglutaminase-2 and lysyl oxidases, respectively.
abstract: Corneal stroma contains an extracellular matrix of orthogonal lamellae formed by parallel and equidistant fibrils with a homogeneous diameter of ~35 nm. This is indispensable for corneal transparency and mechanical functions. However, the mechanisms controlling corneal fibrillogenesis are incompletely understood and the conditions required for lamellar stacking are essentially unknown. Under appropriate conditions, chick embryo corneal fibroblasts can produce an extracellular matrix in vitro resembling primary corneal stroma during embryonic development. Among other requirements, cross-links between fibrillar collagens, introduced by tissue transglutaminase-2, are necessary for the self-assembly of uniform, small diameter fibrils but not their lamellar stacking. By contrast, the subsequent lamellar organization into plywood-like stacks depends on lysyl aldehyde-derived cross-links introduced by lysyl oxidase activity, which, in turn, only weakly influences fibril diameters. These cross-links are introduced at early stages of fibrillogenesis. The enzymes are likely to be important for a correct matrix deposition also during repair of the cornea.
authors.affiliation: From the Institute for Physiological Chemistry and Pathobiochemistry, University Hospital of Münster, 48149 Münster, Germany.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Philipp C
authors.initials: PC
authors.lastname: Uhlig
authors.forename: Eric F
authors.initials: EF
authors.lastname: Eikenberry
authors.forename: Horst
authors.initials: H
authors.lastname: Robenek
authors.forename: Peter
authors.initials: P
authors.lastname: Bruckner
authors.forename: Uwe
authors.initials: U
authors.lastname: Hansen
mesh_terms: D000629:Aminopropionitrile / Q000494:pharmacology; D000818:Animals; D030161:Avian Proteins / Q000737:chemistry / Q000378:metabolism*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D002642:Chick Embryo; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D003319:Corneal Stroma / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism / Q000648:ultrastructure; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D016253:Microscopy, Immunoelectron; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D008249:Protein-Lysine 6-Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D030161:Avian Proteins; D004791:Enzyme Inhibitors; D000629:Aminopropionitrile; D003094:Collagen; D008249:Protein-Lysine 6-Oxidase; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: Collagen; Cornea; Corneal Transparency; Extracellular Matrix; Lysyl Oxidase; Mechanical Stability; Morphog; Post-translational Modification; Suprastructure; Transglutaminases