PMID- 33051415 OWN - NLM STAT- MEDLINE DCOM- 20201015 LR - 20220531 IS - 1672-7347 (Print) IS - 1672-7347 (Linking) VI - 45 IP - 9 DP - 2020 Sept 28 TI - Decreased expression of prohibitin 1 mediates high-mobility group protein 1-induced pulmonary artery endothelial cell injury. PG - 1024-1034 LID - 1672-7347(2020)09-1024-11 [pii] LID - 10.11817/j.issn.1672-7347.2020.190150 [doi] AB - OBJECTIVES: There is a significant increase of high-mobility group protein B1 (HMGB1) in plasma levels of patients with pulmonary hypertension, but the biological significance is still unclear. Anti-proliferative protein 1 (prohibitin 1, PHB1) is an important protein that maintains the homeostasis of vascular cells. This study aimed to investigate the effect of HMGB1 on pulmonary artery endothelial cells and the role of PHB1. METHODS: In vivo experiment: A rat model of pulmonary hypertension induced by monocrotaline (MCT) was constructed. The right ventricular systolic pressure (RVSP), and the weight ratio of right ventricle to left ventricle plus ventricular septum were used to evaluate the success of model. ELISA was used to detect the level of HMGB1 in rat's plasma. Western blotting was used to detect the level of PHB1 in rat's lung tissues. CD31 immunofluorescence was used to detect the integrity of pulmonary vascular endothelium. In vitro experiments: Pulmonary artery endothelial cell (PAEC) was incubated with HMGB1 to observe the effect of HMGB1 on PAEC injury. Overexpression and knockdown of PHB1 were conducted, and the role of PHB1 was investigated by detecting the levels of reative oxygen species and cytochrome c (cyto-c), and the activation of caspase-3. RESULTS: Compared with the control group, the level of HMGB1 in the plasma of rats with pulmonary hypertension was significantly increased (P<0.05), and the expression of PHB1 in the lung tissue was decreased accompanied with endothelial dysfunction (P<0.05); HMGB1 incubation damaged the pulmonary artery endothelium and down-regulated PHB1 expression (P<0.05), while overexpression of PHB1 reduced the PAEC damage and oxidative stress induced by HMGB1 (P<0.05). Meanwhile, PHB1 reduced HMGB1-induced cyto-c expression and caspase-3 cleavage by inhibiting oxidative stress (P<0.05). CONCLUSIONS: The down-regulation of PHB1 expression mediates HMGB1-induced PAEC injury, which is related to the induction of oxidative stress, the increase of cyto-c release, and the promotion of caspase-3 cleavage. FAU - Xu, Yizhou AU - Xu Y AD - Department of Cardiology, Third Xiangya Hospital, Central South University, Changsha 410013. xyz-27366508@qq.com. FAU - Ye, Chen AU - Ye C AD - Xiangya School of Pharmaceutical Science, Central South University, Changsha 410078. FAU - Tang, Lei AU - Tang L AD - Xiangya School of Pharmaceutical Science, Central South University, Changsha 410078. FAU - Pan, Bingjie AU - Pan B AD - Xiangya School of Pharmaceutical Science, Central South University, Changsha 410078. FAU - Li, Ying AU - Li Y AD - Department of Health Management, Third Xiangya Hospital, Central South University, Changsha 410013, China. lydia0312@csu.edu.cn. LA - eng LA - chi GR - JY201709/the "New Xiangya Talent Project" of the Third Xiangya Hospital, Cenctral South University, China/ PT - Journal Article TT - PHB1表达下调介导HMGB1促肺动脉内皮细胞损伤. PL - China TA - Zhong Nan Da Xue Xue Bao Yi Xue Ban JT - Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences JID - 101230586 RN - 0 (HMGB1 Protein) RN - 0 (PHB protein, human) RN - 0 (Prohibitins) RN - 0 (Repressor Proteins) SB - IM MH - Animals MH - Endothelial Cells MH - *HMGB1 Protein/genetics MH - Humans MH - Prohibitins MH - Pulmonary Artery MH - Rats MH - *Repressor Proteins/genetics OTO - NOTNLM OT - high-mobility group protein 1 OT - prohibitin OT - pulmonary artery endothelial cells OT - pulmonary artery hypertension EDAT- 2020/10/15 06:00 MHDA- 2020/10/21 06:00 CRDT- 2020/10/14 09:13 PHST- 2020/10/14 09:13 [entrez] PHST- 2020/10/15 06:00 [pubmed] PHST- 2020/10/21 06:00 [medline] AID - 1672-7347(2020)09-1024-11 [pii] AID - 10.11817/j.issn.1672-7347.2020.190150 [doi] PST - ppublish SO - Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2020 Sept 28;45(9):1024-1034. doi: 10.11817/j.issn.1672-7347.2020.190150.