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Dillon Hawley, Hema Aluri, Michael Mingueneau, Jian Ding, Takeshi Umazume, William Thomas, Sabrina Campbell, Suharika Thotakura, Helen P Makarenkova, Driss Zoukhri; Lacrimal gland inflammation deregulates extracellular matrix remodeling and alters molecular signature of epithelial stem/progenitor cells. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4920.
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© ARVO (1962-2015); The Authors (2016-present)
The adult lacrimal gland 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 lacrimal glands. This study compares changes in the cell adhesion and cell matrix molecules and stem cell transcription factors in the lacrimal glands of healthy mice and the lacrimal glands of two mouse models of Sjögren’s syndrome: non-obese diabetic (NOD) and MRL-lpr/lpr (MRL/lpr) mice during early stages of inflammation.
The lacrimal glands from 12-13 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 qRT PCR and QRT PCR Arrays, histology, immunohistochemistry, and western blotting. In addition we analyzed gene expression in regenerating BALB/c mice lacrimal glands using RNA-seq and qRT PCR. Injury to the lacrimal gland was induced via intraglandular injection of interleukin 1 (IL-1). The lacrimal glands were removed 1, 2, 3, 5, 7, and 14 days post injury and RNA was extracted.
The Extracellular Matrix & Adhesion Molecules RT-PCR array combined with protein expression data revealed changes in the expression of integrins, matrix metalloproteinases and other molecules, which are largely associated with invasion, attachment, and expansion of lymphocytes and other inflammatory immune cells. Changes in the stem cell transcription factors revealed substantial decreases in expression of transcription factors associated with epithelial stem/progenitor cell lineage. Regenerating lacrimal glands showed similar expression pattern of cell adhesion and matrix molecules, while expression of transcription factors associated with regulation of stem/progenitor cell renewal was increased.
We conclude that expression of several important ECM components is significantly modulated in the lacrimal glands 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 lacrimal gland stem/progenitor cells and therefore lacrimal gland regeneration.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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