Anti-Ro/SSA autoantibody-mediated regulation of extracellular matrix fibulins in human epithelial cells of the salivary gland.
OBJECTIVE
The fibulins are a family of extracellular matrix (ECM) molecules that regulate the organ shape along with other growth factors and stromal cells and have recently been shown to be involved in a variety of cellular functions including proliferation, migration, differentiation, and survival. Important changes in acinar and ductal morphology and function, together with pronounced ECM remodelling, are detectable in the labial salivary glands (LSGs) of patients with Sjögren's syndrome (SS). Here we report the in vitro expression of the recently identified ECM proteins fibulin-6 and fibulin-7 by human salivary gland epithelial cells (SGECs). The ability of anti-Ro/SSA autoantibodies (Abs) to modulate fibulin-6 and fibulin-7 expression was investigated.


METHODS
Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and real-time PCR were used to analyse fibulin-6 and fibulin-7 mRNA expression. Confocal microscopy and fluorescence-activated cell sorting (FACS) were used to study expression of the proteins in primary human SGEC cultures, established from biopsies of minor LSGs, in both untreated control cells and anti-Ro/SSA Abs-treated cells.


RESULTS
The methods used show the expression of fibulin-6 and fibulin-7 in SGECs. Treatment of cells with anti-Ro/SSA Abs results in a down-regulation of fibulin-6 mRNA expression whereas no significant differences were observed in fibulin-7 expression between untreated and treated cells.


CONCLUSIONS
Dysregulation of fibulin expression in SGECs by anti-Ro/SSA Abs may contribute to disorganization of the ECM environment and thus cause injury to the salivary gland architecture and functionality observed in SS.
Lisi
S
S
Department of Human Anatomy and Histology, University of Bari, Bari, Italy.
D'Amore
M
M
Scagliusi
P
P
Mitolo
V
V
Sisto
M
M
D023102:Anoikis / Q000276:immunology; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology*; D001706:Biopsy; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000276:immunology; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D005109:Extracellular Matrix / Q000276:immunology*; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D066298:In Vitro Techniques; D012469:Salivary Glands / Q000166:cytology / Q000276:immunology*; D012859:Sjogren's Syndrome / Q000276:immunology*
D000974:Antibodies, Antinuclear; D002135:Calcium-Binding Proteins; C524759:FBLN7 protein, human; C488168:HMCN1 protein, human; D007136:Immunoglobulins; C035356:SS-A antibodies