Umazume Takeshi, Thomas William M, Campbell Sabrina, Aluri Hema, Thotakura Suharika, Zoukhri Driss, Makarenkova Helen P
Department of Cell and Molecular Biology The Scripps Research Institute, La Jolla, California, United States.
Department of Diagnosis and Health Promotion, Tufts University School of Dental Medicine, Boston, Massachusetts, United States.
Invest Ophthalmol Vis Sci. 2015 Dec;56(13):8392-402. doi: 10.1167/iovs.15-17477.
The adult lacrimal gland (LG) is highly regenerative and is able to repair itself even after substantial damage; however, this ability to regenerate is lost with the development of dry eye conditions in chronically inflamed LGs.This study compares changes in the cell adhesion and cell matrix molecules and stem cell transcription factors in the LGs of healthy mice and of two mouse models of Sjögren's syndrome: nonobese diabetic (NOD) and MRL-lpr/lpr (MRL/lpr) mice during the early stage of inflammation.
The LGs from 12- to 13-week-old female MRL/lpr and male NOD mice along with their respective control strains were harvested and divided into three pieces and processed for quantitative (q) RT-PCR and qRT-PCR Arrays, histology, immunohistochemistry, and Western blotting.
The extracellular matrix (ECM) and adhesion molecules RT2-PCR array combined with protein expression data revealed changes in the expression of integrins, matrix metalloproteinases, and other molecules, which are associated largely with invasion, attachment, and expansion of the lymphocytic cells, whereas changes in the stem cell transcription factors revealed substantial decrease in expression of transcription factors associated with epithelial stem/progenitor cell lineage.
We concluded that the expression of several important ECM components is significantly deregulated in the LG of two murine models of Sjögren's syndrome, suggesting an alteration of the epithelial stem/progenitor cell niche. This may result in profound effects on localization, activation, proliferation, and differentiation of the LG stem/progenitor cells and, therefore, LG regeneration.
成年泪腺具有高度再生能力，即使在遭受严重损伤后也能自我修复；然而，随着慢性炎症性泪腺中干眼症的发展，这种再生能力会丧失。本研究比较了健康小鼠以及两种干燥综合征小鼠模型（非肥胖糖尿病（NOD）小鼠和MRL-lpr/lpr（MRL/lpr）小鼠）在炎症早期泪腺中细胞黏附分子、细胞基质分子和干细胞转录因子的变化。
收集12至13周龄雌性MRL/lpr小鼠和雄性NOD小鼠及其各自对照品系的泪腺，切成三块，进行定量（q）RT-PCR和qRT-PCR芯片分析、组织学、免疫组织化学及蛋白质印迹分析。
细胞外基质（ECM）和黏附分子RT2-PCR芯片结合蛋白质表达数据显示，整合素、基质金属蛋白酶和其他分子的表达发生了变化，这些变化主要与淋巴细胞的侵袭、附着和扩增有关，而干细胞转录因子的变化显示，与上皮干细胞/祖细胞谱系相关的转录因子表达大幅下降。
我们得出结论，在两种干燥综合征小鼠模型的泪腺中，几种重要的ECM成分的表达明显失调，这表明上皮干细胞/祖细胞生态位发生了改变。这可能会对泪腺干细胞/祖细胞的定位、激活、增殖和分化产生深远影响，进而影响泪腺再生。
