ArticleArthritis and rheumatism2011
A secretagogue-small interfering RNA conjugate confers resistance to cytotoxicity in a cell model of Sjögren's syndrome.
Article in Arthritis and rheumatism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Beyond inflammation: siRNA strategies for precision targeting in rheumatological disorders.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Cellular Targeting of Oligonucleotides by Conjugation with Small Molecules.Molecules (Basel, Switzerland) · 2020Review
- Interleukin-6 inhibits apoptosis of exocrine gland tissues under inflammatory conditions.Cytokine · 2015Article
- Interleukin-7 enhances the Th1 response to promote the development of Sjögren's syndrome-like autoimmune exocrinopathy in mice.Arthritis and rheumatism · 2013Article
- Nanoparticle-mediated gene silencing confers radioprotection to salivary glands in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- RNAi Therapeutics in Autoimmune Disease.Pharmaceuticals (Basel, Switzerland) · 2013Article
- T Cell-Associated Cytokines in the Pathogenesis of Sjögren's Syndrome.Journal of clinical & cellular immunology · 2013Article
- MicroRNAs and autoimmunity.Current opinion in immunology · 2012Review
- Muscarinic type 3 receptor induces cytoprotective signaling in salivary gland cells through epidermal growth factor receptor transactivation.Molecular pharmacology · 2012Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveSjögren's syndrome (SS) is characterized by xerophthalmia and xerostomia resulting from loss of secretory function due to immune cell infiltration in lacrimal and salivary glands. Current therapeutic strategies for SS use secretagogues to induce secretion via muscarinic receptor stimulation. The purpose of this study was to create a secretagogue-small interfering RNA (siRNA) conjugate to deliver siRNA into cells via receptor-mediated endocytosis, thereby altering epithelial cell responses to external cues, such as proinflammatory or death signals, while simultaneously stimulating secretion.
methodsBased on our expertise with type 3 muscarinic receptor (M3), we used carbachol, a ligand specific for muscarinic receptor, as the secretagogue. Carbachol was synthesized with an active choline group and was conjugated with an siRNA that targets caspase 3. A human salivary gland (HSG) cell line was used to test the efficacy of this secretagogue-siRNA conjugate.
resultsLipofectamine transfection of the conjugate into HSG cells resulted in a 78% reduction in the expression of the caspase 3 gene, while external conjugate treatment of HSG cells resulted in intracellular calcium release and induction of endocytosis at levels similar to those of carbachol stimulation, indicating that the siRNA and carbachol portions of the conjugate retained their function after conjugation. HSG cells treated with conjugate (without Lipofectamine transfection) exhibited a 50% reduction in caspase 3 gene and protein expression, indicating that our conjugate was effective in delivering functional siRNA into cells via receptor-mediated endocytosis. Furthermore, tumor necrosis factor α-induced apoptosis was significantly reduced in conjugate-treated cells.
conclusionOur secretagogue-siRNA conjugate prevented cytokine-induced apoptosis in salivary gland epithelial cells, which is critical to maintaining fluid secretion and potentially reversing the clinical hallmark of SS.
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