Involvement of specific laminins and nidogens in the active remodeling of the basal lamina of labial salivary glands from patients with Sjögren's syndrome.
OBJECTIVE
To investigate remodeling of the basal lamina of labial salivary glands (LSGs) from patients with Sjögren's syndrome (SS) by analyzing the expression of specific components that participate in its assembly and attachment to acinar and ductal cells.


METHODS
Two groups of SS patients with similar levels of remnant glandular tissue but with low and high levels of interacinar fibrosis, respectively, were studied. The expression of laminin alpha1, alpha4, and gamma2 chains and nidogens was examined at the messenger RNA (mRNA) and protein levels. Nidogens 1 and 2 were also studied in situ by immunohistochemistry.


RESULTS
Increases in the amount of mRNA and protein for both the processed and unprocessed laminin gamma2-chain were more pronounced in patients with low interacinar fibrosis. Increases in the protein levels of laminin alpha1 and alpha4 chains were observed in patients with low interacinar fibrosis, but not in those with high interacinar fibrosis. Nidogen mRNA and protein levels were similar in SS patients and controls. Interestingly, high levels of nidogen degradation were observed in patients with low interacinar fibrosis. Nidogens were readily detected by immunofluorescence in the basal lamina of the capillaries and stroma in SS patients, but were less apparent in the basal lamina of the acini and ducts.


CONCLUSIONS
These results suggest that the basal lamina of LSGs from patients with SS is undergoing active remodeling, such that alterations are less evident in patients who have advanced morphologic signs of the disease (high interacinar fibrosis). Nidogen proteolysis might account for the disorganization of the basal lamina that is typically observed in LSGs from SS patients, assuming that cleavage impairs their ability to crosslink type IV collagen and laminin networks.
Kwon
Yoon-Jeoung
YJ
University of Chile, Santiago, Chile.
Pérez
Paola
P
Aguilera
Sergio
S
Molina
Claudio
C
Leyton
Lisette
L
Alliende
Cecilia
C
Leyton
Cecilia
C
Brito
Mónica
M
Romo
Rafael
R
González
María-Julieta
MJ
D000328:Adult; D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D005455:Fluorescent Antibody Technique; D006801:Humans; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D012470:Salivary Glands, Minor / Q000378:metabolism* / Q000473:pathology*; D012859:Sjogren's Syndrome / Q000378:metabolism* / Q000473:pathology*
D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; C501369:LAMA4 protein, human; C400567:LAMC2 protein, human; D007797:Laminin; D008562:Membrane Glycoproteins; C114729:NID2 protein, human; D012333:RNA, Messenger; C029967:nidogen; C084098:laminin A