Abstract
BackgroundTo examine the activity of the mammalian target of rapamycin (mTOR) pathway and its regulators, transforming growth factor (TGF)-β1 and phosphatase and tensin homolog (PTEN), in minor salivary gland biopsies of Sjogren’s syndrome (SS) and systemic sclerosis (SSc) patients.MethodsWe retrospectively evaluated SS, SSc, and SS-SSc overlap patients admitted to our outpatient rheumatology clinic between January 2007 and December 2015 who underwent a minor salivary gland biopsy. Patient demographics and some clinical features were obtained from hospital records. Immunohistochemistry was used to analyze total mTOR, total PTEN, and TGF-β1 expression in the biopsied tissues. The biopsy specimens were also examined for the presence and degree of fibrosis.ResultsMinor salivary gland biopsies of 58 SS, 14 SSc, and 23 SS-SSc overlap patients were included in the study. There was no significant difference in mTOR expression between these groups (P = 0.622). PTEN protein was expressed in 87.2% of patients with SS, 57.9% with overlap syndrome, and 100% of the SSC patients, and these differences were statistically different (P = 0.023). Although ductal epithelial TGF-β1 expression was similar between the groups (P = 0.345), acinar cell expression was found to be more frequent in the SSc (72.7%) and overlap patients (85.7%) in comparison with the SS cases (58.2%; P = 0.004).ConclusionmTOR may be one of the common pathways in the pathology of both SS and SSc. Hence, there may be a role for mTOR inhibitors in the treatment of both diseases. Additionally, PTEN and TGF-β1 expression may be a distinctive feature of SSc.
Highlights
To examine the activity of the mammalian target of rapamycin pathway and its regulators, transforming growth factor (TGF)-β1 and phosphatase and tensin homolog (PTEN), in minor salivary gland biopsies of Sjogren’s syndrome (SS) and systemic sclerosis (SSc) patients
The mammalian target of rapamycin (mTOR) complex includes two multiprotein complexes, mTOR complex 1 and mTOR complex 2 [6]. mTORC1 activates S6 kinase 1 (S6K1) and eukaryotic translation initiation factor 4E which are responsible for Messenger ribonucleic acid (mRNA) translation [5]. mTOR regulates cell survival and is stimulated by growth factors, nutrients, stress signals, phosphoinositol-3-kinase (PI3K), mitogenactivated protein kinase (MAPK), adenosine monophosphate (AMP), and adenosine monophosphate-activated protein kinase (AMPK). mTORC2 regulates the actin cytoskeleton and activates protein kinase C (PKC)-α and Protein kinase B (Akt) [6]. mTOR multiprotein complexes have a positive effect on fibrotic interleukins (ILs)
Formalin-fixed Minor salivary gland biopsy (MSGB) sections from 58 patients with SS, 16 with SSc, and 23 with SSc/ SS overlap syndrome were initially included in the study samples
Summary
To examine the activity of the mammalian target of rapamycin (mTOR) pathway and its regulators, transforming growth factor (TGF)-β1 and phosphatase and tensin homolog (PTEN), in minor salivary gland biopsies of Sjogren’s syndrome (SS) and systemic sclerosis (SSc) patients. Soypaçacı et al Arthritis Research & Therapy (2018) 20:170 synthesize type I collagen and alpha smooth muscle actin (α-SMA) [4] Increased profibrotic mediators, such as transforming growth factor (TGF)-β, and increased mammalian target of rapamycin (mTOR) activity have been reported in dermal fibroblasts of SSc patients [4, 5]. Decreased intracellular levels of PTEN cause PI3K/ Akt/mTOR pathway activation and increase cell proliferation, survival, adhesion, migration, and angiogenesis [7]. TGF-β can both enhance and suppress PTEN, an effect that depends on Ras/ERK pathway activation [7]
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