Serum S100A12 levels: Possible association with skin sclerosis and interstitial lung disease in systemic sclerosis

Abstract

Systemic sclerosis (SSc) is a multisystem autoimmune and vascular disease resulting in multiple organ fibrosis with unknown aetiology. 1 It is generally accepted that an orchestrated complex network of signalling pathways drives a common SSc-specific pathological cascade across multiple organs, 2 which can be affected by organ-specific disease modifiers. 3-5 Recently, damage-associated molecular patterns (DAMPs) have drawn attention as molecules underlying SSc development. 6-9 DAMPs are evolutionally conserved endogenous molecules normally localized inside cells. Upon cellular stress or injury, DAMPs are released into the extracellular space from damaged cells, subsequently activating innate immune cells. The S100A protein family, a

Preeclampsia: Cardiotonic Steroids, Fibrosis, Fli1 and Hint to Carcinogenesis

“…The inhibition of Fli1, a member of the erythroblast transformation specific (ETS) family, is critical for MBG-induced fibrosis [ 32 ]. Fli1 acts as a negative regulator of collagen-1 synthesis and it competes with another transcription factor, ETS-1, to maintain a balance between stimulation and repression of the collagen-1 gene [ 35 , 36 ]. The Na/K-ATPase/Src/EGFR complex begins a signal cascade, which activates phospholipase C (PLC) resulting in the phosphorylation of PKCδ and its translocation to the nucleus.…”

“…In pregnant rats, an increase in the MBG content caused by the consumption of NaCl was accompanied by the development of typical symptoms of PE including increased blood pressure, proteinuria and a decreased weight and size of fetuses [ 39 ]. Taking into account that MBG stimulates the synthesis of collagen, the development of fibrosis in the placenta and umbilical arteries of patients with PE is accompanied by the increased production of MBG and a substantial suppression of Fli1 [ 36 ], as well as that, in PE, vascular stiffness is based on elevated MBG levels [ 33 , 40 ], one can conclude that MBG is one of the major factors involved in the pathogenesis of PE through the induction of vascular fibrosis. In addition, it is assumed that blood vessels exposed to the negative effects of PE factors are subsequently more sensitive to damage despite the disappearance of symptoms of PE after the delivery [ 41 ].…”

Preeclampsia: Сardiotonic Steroids, Fibrosis and a Hint to Cancerogenesis

“…Inhibition of Fli1, a nuclear transcription factor, and a member of the ETS family, is critical for MBG-induced fibrosis [32]. Fli1 acts as a negative regulator of collagen-1 synthesis and it competes with another transcription factor, ETS-1, to maintain a balance between stimulation and repression of the collagen-1 gene [35,36]. The Na/K-ATPase/Src/EGFR complex begins a signal cascade, which activates phospholipase C (PLC) resulting in phosphorylation of PKCδ and its translocation to the nucleus.…”

“…In pregnant rats, an increase in MBG content caused by consumption of NaCl was accompanied by the development of typical symptoms of PE, including increased blood pressure, proteinuria, and decreased weight and size of fetuses [39]. Taking into account that MBG stimulates the synthesis of collagen, the development of fibrosis in placenta and umbilical arteries of patients with PE is accompanied by increased production of MBG and substantial suppression of Fli1 [36], and that in PE vascular stiffness is based on elevated MBG level [33,40], one can conclude that MBG is one of the major factors involved in the pathogenesis of PE through induction of vascular fibrosis. In addition, it is assumed that blood vessels exposed to the negative effects of PE factors are subsequently more sensitive to damage, despite the disappearance of symptoms of PE after the delivery [41].…”

In search of the needle in a haystack: Finding a suitable serum biomarker for monitoring disease activity of systemic sclerosis

“…According to the pathogenesis of SSc involving vasculature, innate and adaptive immune system including its particular chemokine‐mediated immune amplification, 134‐136 and various tissue fibrosis pathways, the proposed SSc biomarkers include angiogenesis‐related proteins (such as endostatin, vascular von Willebrand factor, vWF), 137,138 secreted enzymes and proteins of resident and inflammatory cell types (e. g. elastase), 137 damage‐associated molecular patterns (DAMPs such as S100A12), 139 fibroblast (e. g‐ type III procollagen N‐terminal peptide, PIIINTP or matricellular proteins) 137,140 and endothelial (soluble intercellular adhesion molecule‐1, sICAM‐1) 138 activation markers, growth factors and mediators controlling epidermal and dermal differentiation, 141 proinflammatory cytokines, T‐cell (like soluble interleukin‐2 receptor, sIL2R) 138 and B‐cell markers 138 …”