Fig. 6

A schematic diagram illustrating the mechanism of WYHZTL formula in regulating Wnt/β-catenin signaling pathway. When Wnt protein binds to the transmembrane frizzled receptor (Frizzled family member, Frz) and co-receptor LRP on the cell membrane, cytoplasmic disheveled (Dsh) inhibits activity of the Glycogen synthase kinase 3β (GSK3β) which causes the depolymerization of β-catenin destruction complex-Axin/APC/casein kinase Iα (CKIα)/GSK3β. The degradation of β-catenin is inhibited, then enriched in the cytoplasm and entered into the nucleus, which interacts with transcription factor T cell factor/lymphoid enhancer (TCF/LEF) to form a transcription complex that initiates downstream target genes expression. The target genes include cyclin D1, survivin, connective tissue growth factor (CTGF), which results in activation and transformation of fibroblast to myofibroblast. At last, the excess deposition of extracellular matrix (ECM) leads to the occurrence of skin fibrosis. In our present study, we reveal a mechanism of WYHZTL formula in inhibiting Wnt/β-catenin signaling pathway which can ameliorate skin fibrosis in Bleomycin-induced SSc mouse model