Nonmuscle myosin II shRNA inhibit migration and contraction in rat hepatic stellate cells through regulating AKT/mTOR/S6K/4EBP1 signaling pathway [article]

Zhenghong Li, Yun Feng, Ruling Zhang, Peiwen Wang, Lungen Lu, Yuwei Dong
2018 bioRxiv   pre-print
Migration and contraction of activated hepatic stellate cell (HSC) are essential factors for cirrhosis formation and development. Nonmuscle myosin II (NMMII) inhibitor and mammalian target of rapamycin (mTOR) signaling pathway were involved in these key factors. In the currently study, we used LV-RNAi to specifically attenuate mTOR and NMMII in rat HSC. We aimed to examine the effect of mTOR LV-RNAi on the migration and contraction of HSC and explore the crosslink between mTOR cell signal and
more » ... R cell signal and NMMII. Using real-time PCR and western blot, we found that mTOR and the downstream factors including S6K and 4EBP1 all up-regulated with the activation of HSC. mTOR and NMMII LV-RNAi were transfected into activated HSC, the expression of mTOR can be down-regulated by NMMII LV-RNAi significantly, as well as the expression of S6K, 4EBP1, α-SMA and collagen I, but the level of AKT was up-regulated. Then we used Transwell and collagen lattices to examine the NMMII and mTOR LV-RNAi efficiency on HSC migration and contraction, as we hypothesized, both of the LV-RNAi could inhibit HSC migration and contraction significantly. These results indicated that nonmuscle myosin II shRNA inhibit migration and contraction in rat hepatic stellate cells through the regulation of mTOR/S6K/4EBP1 signaling pathway.
doi:10.1101/313601 fatcat:zgktw7onrvhyffb44bfdplyuwy