Oct-1 Mediates ACTH-Induced Proliferation of Vascular Smooth Muscle Cells

摘要

Adrenocorticotrophic hormone(ACTH),a 39-amino acid peptide hormone,has been reported in the appreciation of the proliferation of vascular smooth muscle cells(VSMCs),however,the mechanism in molecular scale supporting the appreciation remains to be elucidated.In this study,we observed that the protein expression levels of ACTH at 24 h after exposure to 15%cyclic stretch were significantly higher than that after 5%cyclic stretch.When VSMCs were treated with 1000 nM ACTH directly,Oct-1 and lamin B1 expression were both up-regulated associating with each other,and the presence of Oct-1 was found shuttling between the cytosol and nucleus.When we silenced Oct-1 expression with RNA interference,the proliferation of VSMCs decreases significantly,which also validates a dominant contribution of Oct-1 in ACTH-induced VSMC proliferation.We further screened the target molecules of Oct-1 related to the proliferation with ingenuity pathway analysis(IPA),and found that superoxide dismutase 1(SOD1)was significantly induced by ACTH stimulation yet suppressed by Oct-1 interference.All these findings in the present study highlight a new molecular mechanism that ACTH up-regulates Oct-1 expression and activates the protein expression of downstream target SOD1,finally induces the VSMC proliferation.The present work proved Octamer transcription factor-1(Oct-1)as a key transcription factor in the mechanical regulation of VSMC proliferation,which in turn,provide a new target for the treatment of hypertension.