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ATF6 Influences Phenotypic Switch Induced by Hypoxia in Rat Pulmonary Artery Smooth Muscle Cells
Tang Weian1,2, Wang Fang2, Yang Junjun2*, Xu Xingxiang1,2*
1The Second Affiliated Hospital of Xiangya, Central South University, Changsha 410013, China; 2Northen Jiangsu Hospital of Yangzhou University, Yangzhou 225001, China
Abstract: Phenotypic switch of pulmonary artery smooth muscle cells (PASMCs) is an important pathophysiological process in hypoxic pulmonary hypertension (HPH). The specific mechanisms of phenotypic switch under hypoxia are not yet fully understood. This study investigated relations between activated transcription factor 6 (ATF6) and phenotypic switch marker α-smooth muscle actin (α-SMA) under hypoxia condition. The first set of questions aimed to detect changes of ATF6 pathway and phenotypic switch at different hypoxia periods， so we cultured PASMCs (pulmonary artery smooth muscle cells) under hypoxia 0 h， 24 h， 48 h， 72 h. Immunofluorescence showed that ATF6 didn’t expresses in nucleus at hypoxia 0 h， but it expresses at hypoxia 24 h. Western blot showed that ATF6 expression rosed up to 146% in hypoxia 48 h compared with hypoxia 0 h group (P<0.05)， expression levels of α-SMA in hypoxia 48 h group decreased to 35% that of hypoxia 0 h group (P<0.05). This results indicated that hypoxia stimulated ATF6 pathway activation and phenotypic switch. In order to assess influences of ATF6 on phenotypic switch， we knocked down ATF6 by siRNA transfection， Western blot showed that α-SMA levels in hypoxia+ATF6 knockdown group were 162% compared with hypoxia control group (P<0.05)， it indicated that hypoxia-induced α-SMA reduction was inhibited by knockdown of ATF6 gene. This above results indicated that hypoxia might lead to phenotypic switch by ATF6 pathway， ATF6 might be a potential target for treatments of HPH.
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