Abstract
Purpose: :
Previous work has revealed age- and inflammatory disease-correlated alterations in apolipoproteins F (Apof) and E (Apoe) in mouse lacrimal gland (LG) along with abnormal lipid deposition. Here we characterize the expression and distribution of apolipoproteins in human LG in comparison to healthy (BALB/c) and Sjögren’s syndrome disease model (NOD) mouse LG.
Methods: :
Microarray was conducted with RNAs prepared from two human male LG groups, young (54 yr avg) and old (77 yr avg) (n=3 per group), and data compared using Partek GS software. Cryosections of LGs from humans of both genders and mouse models were evaluated microscopically using immunofluorescence and Oil Red O.
Results: :
Microarray analysis detected expression of the following genes in human LG: APOC1, APOD, APOE and APOF. In older males, APOC1, APOD and APOE genes were moderately upregulated to 2.6, 1.5 and 1.3 fold while APOF was downregulated to 60% relative to the younger group (p<0.02). ApoE protein was universally detected at the basolateral membrane of acinar cells from different specimens. However, ApoF protein distribution varied markedly in acinar cells. ApoF was observed in some human LGs at the cytoplasmic face of the plasma membrane but beneath basolateral ApoE, rather than the co-localization of the two proteins seen in BALB/c mouse acinar cells. ApoF in acinar cells from other human LG was detected in a dispersed distribution within cytoplasmic and secretory vesicle-like organelles comparable to the pattern in NOD mouse LG. Oil Red O staining showed many adipocytes scattered within human LG but not within mouse LG.
Conclusions: :
The detection of adipocytes and several apolipoprotein mRNAs indicates that the human LG is active in lipid metabolism. ApoF is subject to age-related regulation and its cellular location appears highly variable in human LG, suggesting the possibility of alterations under pathological conditions. The differential location of ApoF relative to ApoE at the basolateral membrane in human LG suggests ApoF and ApoE may coordinate lipid transport using a distinct mechanism in human relative to mouse.
Keywords: gene/expression • lipids • aging