Altered Distribution of Aquaporin 5 and its C-Terminal Binding Protein in the Lacrimal Glands of a Mouse Model for Sjögren's Syndrome

2008 ◽  
Vol 33 (8) ◽  
pp. 621-629 ◽  
Author(s):  
Yoshiki Ohashi ◽  
Kensei Tsuzaka ◽  
Tsutomu Takeuchi ◽  
Yasumasa Sasaki ◽  
Kazuo Tsubota
Keyword(s):  
Mouse Model ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Binding Protein ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Lacrimal Glands ◽  
Aquaporin 5 ◽  
Sjögren‘S Syndrome

scholarly journals Dysregulated Marginal Zone B Cell Compartment in a Mouse Model of Sjögren’s Syndrome with Ocular Inflammation

2018 ◽  
Vol 19 (10) ◽  
pp. 3117 ◽  
Author(s):  
Niharika Singh ◽  
Ian Chin ◽  
Paul Gabriel ◽  
Emily Blaum ◽  
Sharmila Masli
Keyword(s):  
Mouse Model ◽  
Antibody Response ◽  
Sjögren’S Syndrome ◽  
Marginal Zone ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Lacrimal Glands ◽  
Ocular Manifestations ◽  
Sjögren‘S Syndrome

The risk of developing lymphoma in patients with Sjögren’s syndrome (SS) is 44 times higher than in the normal population with the most common lymphomas derived from marginal zone B (MZB) cells. Current understanding of the role of MZB cells in SS is primarily based on salivary gland pathology, while their contextual association with lacrimal glands and ocular manifestations largely remains unknown. We examined this possibility using a SS mouse model (thrombospondin-1 deficient (TSP1−/−)) with well-characterized ocular disease. We determined the frequency, localization, and cytokine profiles of MZB cells and their association with an antibody response in TSP1−/− mice treated with a TSP-derived peptide. A significantly increased frequency of MZB cells was detected in the spleens and lacrimal glands of TSP1−/− mice in comparison to wild-type tissues as detected by immunostaining. An altered cytokine profile of TSP1−/− MZB cells was supportive of T helper 17 (Th17)-related pathogenesis. A significantly reduced antibody response and the splenic MZB compartment against an eye-derived antigen were noted in TSP-derived peptide-treated mice. These changes correspond with the previously reported ability of the peptide to ameliorate SS-related ocular manifestations. Collectively, our results demonstrate dysregulation of MZB cells in TSP1−/− mice and highlight their role in the context of SS-related chronic ocular surface disease.

scholarly journals Delivery of Bone Marrow-Derived Mesenchymal Stem Cells Improves Tear Production in a Mouse Model of Sjögren’s Syndrome

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Hema S. Aluri ◽  
Mahta Samizadeh ◽  
Maria C. Edman ◽  
Dillon R. Hawley ◽  
Helene L. Armaos ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mouse Model ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Aquaporin 5 ◽  
Tear Production ◽  
Sjögren‘S Syndrome

The purpose of the present study was to test the potential of mouse bone marrow-derived mesenchymal stem cells (BD-MSCs) in improving tear production in a mouse model of Sjögren’s syndrome dry eye and to investigate the underlying mechanisms involved. NOD mice (n=20) were randomized to receive i.p. injection of sterile phosphate buffered saline (PBS, control) or murine BD-MSCs (1 × 106 cells). Tears production was measured at baseline and once a week after treatment using phenol red impregnated threads. Cathepsin S activity in the tears was measured at the end of treatment. After 4 weeks, animals were sacrificed and the lacrimal glands were excised and processed for histopathology, immunohistochemistry, and RNA analysis. Following BD-MSC injection, tears production increased over time when compared to both baseline and PBS injected mice. Although the number of lymphocytic foci in the lacrimal glands of treated animals did not change, the size of the foci decreased by 40.5% when compared to control animals. The mRNA level of the water channel aquaporin 5 was significantly increased following delivery of BD-MSCs. We conclude that treatment with BD-MSCs increases tear production in the NOD mouse model of Sjögren’s syndrome. This is likely due to decreased inflammation and increased expression of aquaporin 5.

scholarly journals Dysregulated co-stimulatory molecule expression in a Sjögren’s syndrome mouse model with potential implications by microRNA-146a

2015 ◽  
Vol 68 (2) ◽  
pp. 606-616 ◽  
Author(s):  
Adrienne E. Gauna ◽  
Yun-Jong Park ◽  
Gautam Nayar ◽  
Marelys Onate ◽  
Jun-o Jin ◽  
...  
Keyword(s):  
Mouse Model ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Sjögren‘S Syndrome

scholarly journals Imbalanced Rab3D versus Rab27 increases cathepsin S secretion from lacrimal acini in a mouse model of Sjögren's Syndrome

2016 ◽  
Vol 310 (11) ◽  
pp. C942-C954 ◽  
Author(s):  
Zhen Meng ◽  
Maria C. Edman ◽  
Pang-Yu Hsueh ◽  
Chiao-Yu Chen ◽  
Wannita Klinngam ◽  
...  
Keyword(s):  
Mouse Model ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Cathepsin S ◽  
Secretory Vesicles ◽  
Structured Illumination Microscopy ◽  
Tear Proteins ◽  
Sjögren‘S Syndrome

The mechanism responsible for the altered spectrum of tear proteins secreted by lacrimal gland acinar cells (LGAC) in patients with Sjögren's Syndrome (SS) remains unknown. We have previously identified increased cathepsin S (CTSS) activity as a unique characteristic of tears of patients with SS. Here, we investigated the role of Rab3D, Rab27a, and Rab27b proteins in the enhanced release of CTSS from LGAC. Similar to patients with SS and to the male nonobese diabetic (NOD) mouse model of SS, CTSS activity was elevated in tears of mice lacking Rab3D. Findings of lower gene expression and altered localization of Rab3D in NOD LGAC reinforce a role for Rab3D in suppressing excess CTSS release under physiological conditions. However, CTSS activity was significantly reduced in tears of mice lacking Rab27 isoforms. The reliance of CTSS secretion on Rab27 activity was supported by in vitro findings that newly synthesized CTSS was detected in and secreted from Rab27-enriched secretory vesicles and that expression of dominant negative Rab27b reduced carbachol-stimulated secretion of CTSS in cultured LGAC. High-resolution 3D-structured illumination microscopy revealed microdomains of Rab3D and Rab27 isoforms on the same secretory vesicles but present in different proportions on different vesicles, suggesting that changes in their relative association with secretory vesicles may tailor the vesicle contents. We propose that a loss of Rab3D from secretory vesicles, leading to disproportionate Rab27-to-Rab3D activity, may contribute to the enhanced release of CTSS in tears of patients with SS.

scholarly journals Associations of Anti-Aquaporin 5 Autoantibodies with Serologic and Histopathological Features of Sjögren's Syndrome

2019 ◽  
Vol 8 (11) ◽  
pp. 1863 ◽  
Author(s):  
Jeon ◽  
Lee ◽  
Park ◽  
Kim ◽  
Choi
Keyword(s):  
Sjögren’S Syndrome ◽  
Lupus Erythematosus ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Study Cohort ◽  
Aquaporin 5 ◽  
Histopathological Features ◽  
International Collaborative ◽  
Sjögren‘S Syndrome

Biomarkers to stratify the complex and heterogeneous phenotypes of Sjogren’s syndrome (SS) are needed. We aimed to validate the prevalence of anti-aquaporin 5 (AQP5) IgG in a non-Korean cohort and to optimize the method to screen the anti-AQP5 IgG. The study cohort included 111 primary SS and 43 non-SS Sjögren's International Collaborative Clinical Alliance (SICCA) controls that were obtained from the Sjögren's International Collaborative Clinical Alliance registry, in addition to 35 systemic lupus erythematosus (SLE) and 35 rheumatoid arthritis (RA) phenotypes. Anti-AQP5 IgG was screened by cell-based immunofluorescence cytochemistry (CB-IFC) assay in the absence or presence of epitope peptides, as well as by ELISA using the epitope peptides as coated antigens. Anti-AQP5 IgG specific to an E1 epitope was best at discriminating between SS and non-SS, and the two different methods (CB-IFC and ELISA) presented comparable performance in diagnostic accuracy (0.690 vs. 0.707). Notably, the SLE and RA groups had substantially lower levels of anti-AQP5 IgG than the SS group. In addition, the presence of anti-AQP5_E1 IgG was associated with serologic and histopathological features of SS. In conclusion, a similar prevalence of anti-AQP5 IgG was confirmed in a non-Korean cohort. Screening anti-AQP5 autoantibodies may help to form subgroups of SS for targeted therapy.

scholarly journals Aspirin Triggered Resolvin D1 reduces inflammation and restores saliva secretion in a Sjögren’s syndrome mouse model

Rheumatology ◽  
2019 ◽  
Vol 58 (7) ◽  
pp. 1285-1292 ◽  
Author(s):  
Spencer Dean ◽  
Ching-Shuen Wang ◽  
Kihoon Nam ◽  
Christina L Maruyama ◽  
Bryan G Trump ◽  
...  
Keyword(s):  
Mouse Model ◽  
Sjögren’S Syndrome ◽  
Sjögren's Syndrome ◽  
Sjogren’S Syndrome ◽  
Sjogren's Syndrome ◽  
Resolvin D1 ◽  
Saliva Secretion ◽  
Sjögren‘S Syndrome
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