title: Laminin isoform profiles in salivary glands in Sjögren's syndrome.
abstract: Five different laminin (LM) alpha, four LM-beta, and three LM-gamma chains form the 15-16 currently known approximately 400-900 kDa heterodimeric LM-monomers, which self-assemble in the lamina lucida of the basement membrane (BM) to a network, connected with nidogens and perlecans with the underlying type IV collagen network. In labial salivary glands (LSG), the structurally organizing/polarizing BM separates the tubuloacinar epithelium from the connective tissue stroma but plays regulatory roles as well. Tissue distribution of LM-alpha, -beta, and -gamma chains is described, and application of the known combinatorial rules allows some conclusions also on the corresponding distribution of the LM-trimers. Currently, known integrin (Int) and non integrin (e.g., dystroglycans and Lutheran blood group antigens) LM-receptors are described. LMs are regulated at transcriptional, translational, and posttranslational levels, together with the regulation of alternative splicing, binding partners (assembly), secretion, and degradation. In LSGs, LM-alpha1, -alpha2, and -alpha4 are only found in the acinar (not ductal) BM, LM-alpha4 also in the periductal/ interstitial stroma. Pattern recognition disclosed irregular expression in the acinar BM, suggesting some dynamic and/or regulatory role. It seems that in a female-dominant autoimmune exocrinopathy, Sjögren's syndrome (SS), LM-alpha1 and -alpha2 are decreased, together with their Int alpha1beta1 and alpha2beta1 receptors. Because LM-111/211-to-Int-alpha1beta1/alpha2beta1 interactions play a crucial role in the transdifferentiation of the intercalated duct progenitors to secretory acinar cells, acinar remodeling is impaired in SS. Disturbed hemidesmosomal Int alpha6beta4/LM-332 interactions in SS may lead to acinar cell anoikis. Interestingly, dehydroepiandrosterone (DHEA) prohormone and its intracrine androgenic dihydrotestosterone (DHT) end product upregulate at least Int alpha1beta1/alpha2beta1, whereas LM-alpha1 is upregulated by outside-in LM-111/211-to-Int-alpha1beta1/alpha2beta1 signaling. It seems that LM alterations precede the lymphocyte infiltration, suggesting that acinar BM-Int pathology, perhaps related to endo- and intracrine sex steroid metabolism, represents an early pathogenic phases in SS.
authors: Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland.
authors: Pauliina
authors: P
authors: Porola
authors: Zygmunt
authors: Z
authors: Mackiewicz
authors: Mikael
authors: M
authors: Laine
authors: Gonçalo
authors: G
authors: Baretto
authors: Vasily
authors: V
authors: Stegaev
authors: Yuya
authors: Y
authors: Takakubo
authors: Michiaki
authors: M
authors: Takagi
authors: Mari
authors: M
authors: Ainola
authors: Yrjö T
authors: YT
authors: Konttinen
mesh_terms: D061354:Acinar Cells / Q000378:metabolism / Q000473:pathology; D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology; D015153:Blotting, Western; D054338:Cell Transdifferentiation; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D039222:Integrin alpha1beta1 / Q000378:metabolism; D007797:Laminin / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D020033:Protein Isoforms / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism; D017474:Receptors, Laminin / Q000235:genetics / Q000378:metabolism; D012469:Salivary Glands / Q000378:metabolism* / Q000473:pathology; D012859:Sjogren's Syndrome / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: D024141:Collagen Type IV; D039222:Integrin alpha1beta1; D007797:Laminin; D008562:Membrane Glycoproteins; D020033:Protein Isoforms; D017474:Receptors, Laminin; C029967:nidogen