Anti‐Ro/SSA autoantibody‐mediated regulation of extracellular matrix fibulins in human epithelial cells of the salivary gland

2009, Vol. 38, No. 3 , Pages 198-206 (doi:10.1080/03009740802520722)
1Department of Human Anatomy and Histology
2Department of Internal Medicine and Public Medicine, Section of Rheumatology, University of Bari, Italy
Margherita Sisto, Department of Human Anatomy and Histology, University of Bari, piazza Giulio Cesare 1, I‐70124 Bari, Italy



Objectives: 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.

Conclusion: 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.