Lacrimal Gland Inflammation Deregulates Extracellular Matrix Remodeling and Alters Molecular Signature of Epithelial Stem/Progenitor Cells

Overview

Journal Invest Ophthalmol Vis Sci

Specialty Ophthalmology

Date 2016 Jan 10

PMID 26747770

Citations 14

Authors

Takeshi Umazume

William M Thomas

Sabrina Campbell

Hema Aluri

Suharika Thotakura

Driss Zoukhri

Helen P Makarenkova

Affiliations

Soon will be listed here.

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Citing Articles

Weighted Gene Co-expression Network Analysis and Machine Learning Validation for Identifying Major Genes Related to Sjogren's Syndrome.

Luo Q, Wu K, Li H, Wang H, Wang C, Xia D Biochem Genet. 2024; .

PMID: 38678487 DOI: 10.1007/s10528-024-10750-4.

Klotho Null Mutation Indirectly Leads to Age-Related Lacrimal Gland Degeneration in Mutant Mice.

Wu C, Song D, Lu T, Chen Z, Tsai S, Liu Y Biology (Basel). 2023; 12(10).

PMID: 37887038 PMC: 10604155. DOI: 10.3390/biology12101328.

Ectopic lymphoid structures in the aged lacrimal glands.

Galletti J, Scholand K, Trujillo-Vargas C, Yu Z, Mauduit O, Delcroix V Clin Immunol. 2023; 248:109251.

PMID: 36740002 PMC: 10323865. DOI: 10.1016/j.clim.2023.109251.

Role of FGF10/FGFR2b Signaling in Homeostasis and Regeneration of Adult Lacrimal Gland and Corneal Epithelium Proliferation.

Finburgh E, Mauduit O, Noguchi T, Bu J, Abbas A, Hakim D Invest Ophthalmol Vis Sci. 2023; 64(1):21.

PMID: 36715672 PMC: 9896866. DOI: 10.1167/iovs.64.1.21.

The Effect of Mesenchymal Stem Cells on Dry Eye in Sjogren Syndrome Mouse Model.

Shin S, Yoon S, Kim M, Cheon E, Jeon Y, Lee H Int J Mol Sci. 2023; 24(2).

PMID: 36674547 PMC: 9865485. DOI: 10.3390/ijms24021039.

References

Zoukhri D . Mechanisms involved in injury and repair of the murine lacrimal gland: role of programmed cell death and mesenchymal stem cells. Ocul Surf. 2010; 8(2):60-9. PMC: 3225027. DOI: 10.1016/s1542-0124(12)70070-8. View

Zoukhri D, Ko S, Stark P, Kublin C . Roles of caspase 1 and extracellular signal-regulated kinase in inflammation-induced inhibition of lacrimal gland protein secretion. Invest Ophthalmol Vis Sci. 2008; 49(10):4392-8. PMC: 2568975. DOI: 10.1167/iovs.08-1830. View

Huang H, Chen P, Yu C, Chuang C, Stone L, Hsiao W . Epithelial cell adhesion molecule (EpCAM) complex proteins promote transcription factor-mediated pluripotency reprogramming. J Biol Chem. 2011; 286(38):33520-32. PMC: 3190890. DOI: 10.1074/jbc.M111.256164. View

Vais V, Vangeli I, Bakeeva L . Ultrastructural changes in ageing lacrimal gland in Wistar rats. Bull Exp Biol Med. 2014; 157(2):268-72. DOI: 10.1007/s10517-014-2542-9. View

Hassiotou F, Hepworth A, Beltran A, Mathews M, Stuebe A, Hartmann P . Expression of the Pluripotency Transcription Factor OCT4 in the Normal and Aberrant Mammary Gland. Front Oncol. 2013; 3:79. PMC: 3622876. DOI: 10.3389/fonc.2013.00079. View

Peck A, Saylor B, Nguyen L, Sharma A, She J, Nguyen C . Gene expression profiling of early-phase Sjögren's syndrome in C57BL/6.NOD-Aec1Aec2 mice identifies focal adhesion maturation associated with infiltrating leukocytes. Invest Ophthalmol Vis Sci. 2011; 52(8):5647-55. PMC: 3176054. DOI: 10.1167/iovs.11-7652. View

Doyle M, Boggs L, Attia R, Cooper L, Saban D, Nguyen C . Autoimmune dacryoadenitis of NOD/LtJ mice and its subsequent effects on tear protein composition. Am J Pathol. 2007; 171(4):1224-36. PMC: 1988872. DOI: 10.2353/ajpath.2007.070388. View

Hiraoka M, Saito I, Tsubota K, Sugai S, Miyasaka N . Augmented expression of CD44 splice variants in lymphoproliferative disorder of the lacrimal gland in Sjögren's syndrome. Jpn J Ophthalmol. 1997; 41(5):312-8. DOI: 10.1016/s0021-5155(97)00072-5. View

Zoukhri D, Macari E, Choi S, Kublin C . c-Jun NH2-terminal kinase mediates interleukin-1beta-induced inhibition of lacrimal gland secretion. J Neurochem. 2005; 96(1):126-35. PMC: 1414092. DOI: 10.1111/j.1471-4159.2005.03529.x. View

10.

Blum R, Gupta R, Burger P, Ontiveros C, Salm S, Xiong X . Molecular signatures of prostate stem cells reveal novel signaling pathways and provide insights into prostate cancer. PLoS One. 2009; 4(5):e5722. PMC: 2684642. DOI: 10.1371/journal.pone.0005722. View

11.

Govindarajan V, Ito M, Makarenkova H, Lang R, Overbeek P . Endogenous and ectopic gland induction by FGF-10. Dev Biol. 2000; 225(1):188-200. DOI: 10.1006/dbio.2000.9812. View

12.

Xu B, Berberian J, Michie S . Lymphocyte migration to inflamed lacrimal glands is mediated by vascular cell adhesion molecule-1/alpha(4)beta(1) integrin, peripheral node addressin/l-selectin, and lymphocyte function-associated antigen-1 adhesion pathways. Am J Pathol. 2001; 159(2):671-81. PMC: 1850552. DOI: 10.1016/s0002-9440(10)61738-5. View

13.

Nguyen D, Toshida H, Schurr J, Beuerman R . Microarray analysis of the rat lacrimal gland following the loss of parasympathetic control of secretion. Physiol Genomics. 2004; 18(1):108-18. PMC: 2835548. DOI: 10.1152/physiolgenomics.00011.2004. View

14.

Ordonez P, Di Girolamo N . Limbal epithelial stem cells: role of the niche microenvironment. Stem Cells. 2011; 30(2):100-7. DOI: 10.1002/stem.794. View

15.

Lim M, Goldstein M, Tuli S, Schultz G . Growth factor, cytokine and protease interactions during corneal wound healing. Ocul Surf. 2006; 1(2):53-65. DOI: 10.1016/s1542-0124(12)70128-3. View

16.

Abram C, Roberge G, Pao L, Neel B, Lowell C . Distinct roles for neutrophils and dendritic cells in inflammation and autoimmunity in motheaten mice. Immunity. 2013; 38(3):489-501. PMC: 3613338. DOI: 10.1016/j.immuni.2013.02.018. View

17.

Arafat S, Suelves A, Spurr-Michaud S, Chodosh J, Foster C, Dohlman C . Neutrophil collagenase, gelatinase, and myeloperoxidase in tears of patients with stevens-johnson syndrome and ocular cicatricial pemphigoid. Ophthalmology. 2013; 121(1):79-87. PMC: 3920830. DOI: 10.1016/j.ophtha.2013.06.049. View

18.

Crosby L, Waters C . Epithelial repair mechanisms in the lung. Am J Physiol Lung Cell Mol Physiol. 2010; 298(6):L715-31. PMC: 2886606. DOI: 10.1152/ajplung.00361.2009. View

19.

Petznick A, Madigan M, Garrett Q, Sweeney D, Evans M . Contributions of ocular surface components to matrix-metalloproteinases (MMP)-2 and MMP-9 in feline tears following corneal epithelial wounding. PLoS One. 2013; 8(8):e71948. PMC: 3747068. DOI: 10.1371/journal.pone.0071948. View

20.

Chen Z, Huang J, Liu Y, Dattilo L, Huh S, Ornitz D . FGF signaling activates a Sox9-Sox10 pathway for the formation and branching morphogenesis of mouse ocular glands. Development. 2014; 141(13):2691-701. PMC: 4067963. DOI: 10.1242/dev.108944. View