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

人气道平滑肌细胞（hASMC）的异常增殖和迁移在儿童哮喘中起关键作用。我们调查的影响六成分-小庆龙煎剂（SXD）的转化生长因子（TGF） - β 1刺激HASMC。通过CCK-8和transwell测定法测定TGF- β1诱导的hASMC的细胞存活力和迁移。RT-qPCR和Western blotting检测FK506结合蛋白51（FKBP51），蛋白激酶B（AKT），p-AKT的表达。另外，进行FKBP51过表达（oeFKBP51）和FKBP51敲低（siFKBP51）以进一步证实结果。SXD剂量依赖性地抑制了TGF- β1诱导的hASMC的细胞增殖和迁移。转化生长因子1以时间依赖性方式显着抑制FKBP51的mRNA和蛋白质水平。然而，与TGF- β1组相比，SXD增加了FKBP51的表达，而抑制了p-AKT。此外，oeFKBP51和SXD均降低了TGF- β1诱导的hASMC的迁移能力，并提高了FKBP51的表达但降低了p-AKT。最终，siFKBP51促进了细胞迁移并引起了hASMC中p-AKT的上调，但SXD可以逆转这些变化。SXD可以通过激活FKBP51 / AKT信号转导抑制hASMC的增殖和迁移，为儿童哮喘治疗提供新的靶点。

缩写： SXD，六成分小青龙汤；hASMC，人气道平滑肌细胞；TGF- β1，转化生长因子β1；ECM，细胞外基质；ERK，细胞外信号调节激酶；JNK，C军NH（2）端激酶；FKBP51，FK506结合蛋白51；中医药；oeFKBP51，FK506结合蛋白51过表达; PI3K，磷脂酰肌醇3-激酶；AKT，蛋白激酶B；p-AKT，磷酸化AKT；qRT-PCR，实时荧光定量PCR；中医药；CCK-8，细胞计数试剂盒8，SRA，类固醇抗性哮喘