Androgens and integrins in salivary glands in Sjogren's syndrome.
OBJECTIVE
Laminin alpha1-chain normally induces intercalated duct progenitors to differentiate to acinar cells through integrin (INT) alpha1ss1 and alpha2ss1 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 alpha1 chain or its cellular alpha1 or alpha2 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 alpha1 chain and INT alpha1 and alpha2 subunits were studied using quantitative reverse-transcription real-time polymerase chain reaction and INT alpha1 and alpha2 subunits using immunofluorescence staining.


RESULTS
INT alpha1-subunit and alpha2-subunit messenger RNA (mRNA) levels were increased in intercalated duct and acinar cells by DHEA and testosterone. In contrast, laminin alpha1-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.


CONCLUSIONS
Androgens increased INT alpha1 and alpha2 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.
Porola
Pauliina
P
Department of Medicine, Biomedicum 1, Helsinki, Helsinki University Central Hospital, PO Box 700, FIN-00029 HUS, Helsinki, Finland.
Laine
Mikael
M
Virtanen
Ismo
I
Pöllänen
Raimo
R
Przybyla
Beata D
BD
Konttinen
Yrjö T
YT
D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002460:Cell Line; D003687:Dehydroepiandrosterone / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D006801:Humans; D039423:Integrin alpha1 / Q000235:genetics / Q000378:metabolism*; D039421:Integrin alpha2 / Q000235:genetics / Q000378:metabolism*; D007797:Laminin / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D018987:Salivary Ducts / Q000187:drug effects / Q000378:metabolism; D012470:Salivary Glands, Minor / Q000187:drug effects / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000235:genetics / Q000378:metabolism*; D013739:Testosterone / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D055815:Young Adult
D039423:Integrin alpha1; D039421:Integrin alpha2; D007797:Laminin; D012333:RNA, Messenger; C084098:laminin A; D013739:Testosterone; D003687:Dehydroepiandrosterone