Role of the mTOR pathway in minor salivary gland changes in Sjogren’s syndrome and systemic sclerosis

Abstract

[...]there may be a role for mTOR inhibitors in the treatment of both diseases. The mTOR complex includes two multiprotein complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) [6]. mTORC1 activates S6 kinase 1 (S6K1) and eukaryotic translation initiation factor 4E (eIF4E) which are responsible for mRNA translation [5]. mTOR also regulates cell survival and is stimulated by growth factors, nutrients, stress signals, phosphoinositol-3-kinase (PI3K), mitogen-activated 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 Akt (protein kinase B, or PKB) [6]. mTOR multiprotein complexes have a positive effect on fibrotic interleukins (ILs). Table 2 Immunohistochemical staining results in the three patient groups (mTOR, PTEN, and TGF-β1 in acinus) Negative Mild positivity Moderate positivity Strong positivity mTOR SS 3 (6) 25 (46) 20 (37) 6 (11) Overlap syndrome 0 11 (55) 9 (45) 0 SSc 1 (9) 4 (36) 5 (46) 1 (9) PTEN SS 6 (13) 23 (49) – 18 (38) Overlap syndrome 8 (42) 5 (26) – 6 (32) SSc 0 7 (58) – 5 (42) TGF-β1 SS 23 (42) 20 (36) 10 (18) 2 (4) Overlap syndrome 3 (14) 10 (48) 4 (19) 4 (19) SSc 3 (27) 2 (18) 1 (9) 5 (46) All values are shown as n (%) mTOR mammalian target of rapamycin, PTEN phosphatase and tensin homolog, SS Sjogren’s syndrome, SSc systemic sclerosis, TGF transforming growth factor Fibrosis features In general, fibrosis was evident in all of our patient groups but we did not observe severe fibrosis in any MSGB sections. [...]the most important limitation of this study is the lack of a control group. [...]studies with healthy control groups may shed light on the pathogenesis of SSc and SS and may help us to understand the role of the mTOR pathway in the rheumatologic diseases.