Androgens and integrins in salivary glands in Sjögren's syndrome

Abstract

Objective. Laminin α1-chain normally induces intercalated duct progenitors to differentiate to acinar cells through integrin (INT) α1β1 and α2β1 receptors. Maintenance of acinar cells is impaired in Sjögren's syndrome (SS), which is also characterized by low levels of serum and salivary androgens. We hypothesized that androgens normally support salivary gland remodeling by upregulating either laminin α1 chain or its cellular α1 or α2 INT subunit-containing receptors. Methods. Intercalated duct and acinar human salivary gland (HSG) cells and labial salivary gland (LSG) biopsies from healthy controls and patients with SS were cultured without or with sex steroids. Laminin α1 chain and INT α1 and α2 subunits were studied using quantitative reverse-transcription real-time polymerase chain reaction and INT α1 and α2 subunits using immunofluorescence staining. Results. INT α1-subunit and α2-subunit messenger RNA (mRNA) levels were increased in intercalated duct and acinar cells by DHEA and testosterone. In contrast, laminin α1-chain mRNA levels were not affected. The upregulating effect of DHEA on INT subunits was also seen at the protein level. DHEA also increased mRNA levels of both INT subunits in healthy but not SS LSG. Conclusion. Androgens increased INT α1 and α2 subunits in tubuloepithelial cells and in healthy LSG, but in SS salivary glands this androgen regulation was defective, which is likely to contribute to defective outside-in signaling, acinar atrophy, and ductal cell hyperplasia. Copyright © 2010. All rights reserved.