Hepatopulmonary syndrome (HPS) has been classically associated with intrapulmonary vasodilatation (IPVD) and pulmonary vascular remodelling (PVR), which are the key pathophysiological components of HPS and concerned frequently in the studies of HPS. Little is known about the relevance of pulmonary artery smooth muscle cells (PASMCs) migration or the molecular mechanisms of PVR in HPS. Annexin A2 (ANXA2) plays crucial role in HPS-associated PVR and might activate the activity of paxillin which as a regulatory protein participates in the regulation of PASMCs function in PVR. In addition, it has been identified that ANXA2 could influence the cells migration by some important signaling pathways in many diseases, including lung cancer, pulmonary hypertensionand and liver cancer. In this study, we performed scratch wound motility assay, modified boyden chamber, reverse transcription PCR, western blot and co-immunoprecipitation to determine the role of ANXA2 on HPS-associated PVR. We found that HPS rat serum from a common bile duct ligation (CBDL) rat model enhanced the migration of PASMCs and increased the expression of ANXA2 in PASMCs. We reported that ANXA2 and paxillin could form a co-immunoprecipitation. After silencing ANXA2 with siRNA, we found that the up-regulation of paxillin expression, induced by the HPS rat serum, was reversed. Additionally, we found that down-regulation of ANXA2 could significantly inhibit the migration of PASMCs. These findings indicated that down regulation of ANXA2 by siRNA results in the inhibition of the aberrant dysregulation of paxillin and migration of PASMCs, which suggesting a potential therapeutic effect on HPS-associated PVR. (C) 2015 Elsevier Inc. All rights reserved.