A total of 26 of these miRNAs targeted genes involved in pathways connected to the three main features of SSc and to cancer development including Epidermal growth factor (EGF) receptor, ErbB1 downstream, Sphingosine 1 phosphate receptor 1 (S1P1), Activin receptor-like kinase 1 (ALK1), Endothelins, Ras homolog family member A (RhoA), Class I Phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), p38 mitogen-activated protein kinase (MAPK), Ras-related C3 botulinum toxin substrate 1 (RAC1), Transforming growth factor (TGF)-beta receptor, Myeloid differentiation primary response 88 (MyD88) and Toll-like receptors (TLRs) pathways.
In our study, we measured the serum HB-EGF levels of 51 systemic sclerosis (SSc) patients, which showed a significant increase compared with those of 20 normal subjects.
These results indicate that EGF-mediated induction of TGFbetaRII expression occurs at the transcription level, does not require de novo protein synthesis, and involves the PI 3-kinase/Akt signaling pathway, and that abnormal activation of EGF-mediated signaling pathways, including PI 3-kinase or Akt, might play a role in the up-regulation of TGFbetaRII in scleroderma fibroblasts.
Three recombinant peptides accounting for the N-terminal end, proline-rich C region, and epidermal growth factor-like calcium-binding (EGF-cb) domains of fibrillin 1 were used in a radioimmunoassay to screen sera from a large group of SSc and PM/DM patients and ethnically matched controls.