ArticleLaboratory investigation; a journal of technical methods and pathology2013
The Hippo signaling pathway is required for salivary gland development and its dysregulation is associated with Sjogren's syndrome.
Article in Laboratory investigation; a journal of technical methods and pathology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 55 citations in OpenAlex.
- Human Lacrimal Gland Gene Expression.PloS one · 2017Trial
- Significance of Notch Signaling in Salivary Gland Development and Diseases.Journal of clinical medicine · 2025Review
- Primary Sjögren's syndrome: new perspectives on salivary gland epithelial cells.European journal of medical research · 2024Review
- Exploring the Cocktail Factor Approach to Generate Salivary Gland Progenitors through Co-Culture Techniques.Tissue engineering and regenerative medicine · 2024Article
- Research progress on Hippo signaling pathway effector molecules in rheumatic immune system diseases.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- Adipose-derived stem cells postpone the progression of Sjögren's syndrome by upregulating the Hippo signaling pathway.Experimental and therapeutic medicine · 2022Article
- Salivary gland function, development, and regeneration.Physiological reviews · 2022Review
- Reversely immortalized mouse salivary gland cells presented a promising metabolic and fibrotic response upon BMP9/Gdf2 stimulation.Cellular & molecular biology letters · 2022Article
- Regulation of myoepithelial differentiation.PloS one · 2022Article
- Gene expression alterations in salivary gland epithelia of Sjögren's syndrome patients are associated with clinical and histopathological manifestations.Scientific reports · 2021Article
- The Hippo pathway: a renewed insight in the craniofacial diseases and hard tissue remodeling.International journal of biological sciences · 2021Review
- Immune-Intrinsic Myd88 Directs the Production of Antibodies With Specificity for Extracellular Matrix Components in Primary Sjögren's Syndrome.Frontiers in immunology · 2021Article
- Relation Between Immunohistochemical Expression of Hippo Pathway Effectors and Chronic Hepatitis Induced Fibrosis in Egyptian Patients.Turk patoloji dergisi · 2020Article
- Epithelial Cell Lineage and Signaling in Murine Salivary Glands.Journal of dental research · 2019Review
- The Hippo Signaling Pathway in Development and Disease.Developmental cell · 2019Review
- Danger signals in oral cavity-related diseases.Journal of leukocyte biology · 2019Review
- aPKCζ-dependent Repression of Yap is Necessary for Functional Restoration of Irradiated Salivary Glands with IGF-1.Scientific reports · 2018Article
- Current and Emerging Evidence for Toll-Like Receptor Activation in Sjögren's Syndrome.Journal of immunology research · 2018Review
- Myd88 is required for disease development in a primary Sjögren's syndrome mouse model.Journal of leukocyte biology · 2017Article
- Innate immunity in Sjögren's syndrome.Clinical immunology (Orlando, Fla.) · 2017Review
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Sjogren's syndrome (SS) is a complex autoimmune disease that primarily affects salivary and lacrimal glands and is associated with high morbidity. Although the prevailing dogma is that immune system pathology drives SS, increasing evidence points to structural defects, including defective E-cadherin adhesion, to be involved in its etiology. We have shown that E-cadherin has pivotal roles in the development of the mouse salivary submandibular gland (SMG) by organizing apical-basal polarity in acinar and ductal progenitors and by signaling survival for differentiating duct cells. Recently, E-cadherin junctions have been shown to interact with effectors of the Hippo signaling pathway, a core pathway regulating the organ size, cell proliferation, and differentiation. We now show that Hippo signaling is required for SMG-branching morphogenesis and is involved in the pathophysiology of SS. During SMG development, a Hippo pathway effector, TAZ, becomes increasingly phosphorylated and associated with E-cadherin and α-catenin, consistent with the activation of Hippo signaling. Inhibition of Lats2, an upstream kinase that promotes TAZ phosphorylation, results in dysmorphogenesis of the SMG and impaired duct formation. SMGs from non-obese diabetic mice, a mouse model for SS, phenocopy the Lats2-inhibited SMGs and exhibit a reduction in E-cadherin junctional components, including TAZ. Importantly, labial specimens from human SS patients display mislocalization of TAZ from junctional regions to the nucleus, coincident with accumulation of extracellular matrix components, fibronectin and connective tissue growth factor, known downstream targets of TAZ. Our studies show that Hippo signaling has a crucial role in SMG-branching morphogenesis and provide evidence that defects in this pathway are associated with SS in humans.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.