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Liu YR, Ye WL, Zeng XM, Ren WH, Zhang YQ, Mei YA: K+ channels and the cAMP-PKA pathway modulate TGF-beta1-induced migration of rat vascular myofibroblasts. J Cell Physiol. 2008 Sep;216(3):835-43.
Our previous studies have indicated that TGF-beta1 exerts its effect on the expression of A-type potassium channels (I (A)) in rat vascular myofibroblasts by activation of protein kinase C during the phenotypic transformation of vascular fibroblasts to myofibroblasts. In the present study, patch-clamp whole-cell recording and transwell-migration assays were used to examine the effects of TGF-beta1- and phorbol 12-myristate 13-acetate (PMA)-induced expression of I (A) channels on myofibroblast migration and its modulation by the protein kinase A (PKA) pathway. Our results reveal that incubation of fibroblasts with TGF-beta1 or PMA up-regulates the expression of I (A) channels and increases myofibroblast migration. Blocking I (A) channel expression by 4-aminopyridine (4-AP) significantly inhibits TGF-beta1- and PMA-induced myofibroblast migration. Incubation of fibroblasts with forskolin does not result in increased expression of I (A) channels but does cause a slight increase in fibroblast migration at higher concentrations. In addition, forskolin increases the TGF-beta1- and PMA-induced myofibroblast migration but inhibits TGF-beta1- and PMA-induced the expression of I (A) channels. Whole-cell current recordings showed that forskolin augments the delayed rectifier outward K (+) (I (K)) current amplitude of fibroblasts, but not the I (A) of myofibroblasts. Our results also indicate that TGF-beta1- and PMA-induced expression of I (A) channels might be related to increase TGF-beta1- or PMA-induced myofibroblast migration. Promoting fibroblast and myofibroblast migration via the PKA pathway does not seem to involve the expression of I (A) channels, but the modulation of I (K) and I (A) channels might be implicated. |
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