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. 2023 May 15;14:1151246. doi: 10.3389/fimmu.2023.1151246

Figure 1.

Figure 1

Scheme of the Ras signaling pathway that increases in the fibrosis process and SSc disease. PDGF, Anti-PDGFR antibodies can activate MAPK signaling in fibroblasts of SSc patients and cause expression enhancement of involved genes in the fibrosis process and also TGF-β can through both the Smad pathway and non-Smad pathway (PI3k, JNK, and P38) activate fibroblasts, increase the synthesis of collagen, fibronectin and develop fibrosis. TGF-β, Transforming growth factor beta; TβR, Transforming growth factor beta receptor; PDGF, Platelet-derived growth factor; PDGFR, Platelet-derived growth factor receptor; GRB2, Growth factor receptor-bound protein 2; MEK, Mitogen-activated protein kinase kinase; ERK, extracellular signal-regulated kinase; PIP2, Phosphatidylinositol 4; 5-bisphosphate; PIP3, Phosphatidylinositol (3; 4; 5)-triphosphate; PI3K, Phosphoinositide 3-kinases; PTEN, Phosphatase and tensin homolog; TAK1, TGF‐β‐activated kinase 1; MKK, The mitogen-activated protein kinase kinase; PTP, Protein tyrosine phosphatases; NF-κB, Nuclear Factor kappa-light-chain-enhancer of activated B cells; ROS, Reactive oxygen species; ATF2, Activating transcription factor 2.