Six-ingredient-Xiao-qing-long decoction inhibited TGF-β1-induced proliferation and migration of human airway smooth muscle cells by regulating FKBP51/AKT signaling

Abstract

Abnormal proliferation and migration of human airway smooth-muscle cells (hASMC) play crucial roles in child asthma. We investigated the effect of Six-ingredient-Xiao-qing-long decoction (SXD) on the transforming growth factor (TGF)-β1-stimulated hASMC. Cell viability and migration of TGF-β1-induced hASMC were determined by CCK-8 and transwell assays. The expressions of FK506 binding protein 51 (FKBP51), protein kinase B (AKT), p-AKT were determined by RT-qPCR and western blotting. In addition, FKBP51 overexpression (oeFKBP51) and FKBP51 knockdown (siFKBP51) were carried out to further confirm the results. SXD dose-dependently suppressed the cell proliferation and migration of TGF-β1-induced hASMC. TGF-β1 markedly inhibited the mRNA and protein levels of FKBP51 in a time-dependent manner. Nevertheless, compared to the TGF-β1 group, SXD increased the expression of FKBP51 while suppressed p-AKT. Moreover, both oeFKBP51 and SXD reduced the migration ability of TGF-β1-induced hASMC, as well as elevated the expressions of FKBP51 but decreased p-AKT. Finally, siFKBP51 promoted cell migration and caused the up-regulation of p-AKT in hASMC, but SXD could reverse these changes. SXD could suppress the proliferation and migration of hASMC via activating FKBP51/AKT signaling, which may provide a novel possible target for child asthma therapy. Abbreviations: SXD, Six-ingredient-Xiao-qing-long decoction; hASMC, human airway smooth muscle cells; TGF-β1, transforming growth factor β1; ECM, extracellular matrix; ERK, extracellular signal-regulated kinase; JNK, C-Jun NH(2)-terminal kinase; FKBP51, FK506 binding protein 51; TCM, traditional Chinese medicine; oeFKBP51, FK506 binding protein 51 overexpression; PI3K, phosphatidylinositol 3-kinase; AKT, protein kinase B; p-AKT, phosphorylation AKT; qRT-PCR, real-time fluorescence quantitative PCR; TCM, traditional Chinese medicine; CCK-8, Cell Counting Kit-8, SRA, Steroid-resistant asthma