Galectin-3 Mediates Endothelial-to-Mesenchymal Transition in Pulmonary Arterial Hypertension

Li, Tangzhiming1,6; Zha, Lihuang1; Luo, Hui1; Li, Suqi2,3; Zhao, Lin4; He, Jingni1; Li, Xiaohui5; Qi, Qiangqiang1; Liu, Yuwei1; Yu, Zaixin1

2019-08

10.14336/AD.2018.1001

Aging and Disease   影响因子和分区

2152-5250

Galectin-3 (Gal-3) is highly expressed in fibrotic tissue related to diverse etiologies. endothelial-to-mesenchymal transition (EndoMT), A less well studied phenomenon serves as a critical process in pulmonary vascular remodeling associated with the development of pulmonary arterial hypertension (PAH). EndoMT is hypothesized to contribute to the over-proliferation of alpha SMA positive cells. We aim to investigate the potential role of Gal-3 in regulating EndoMT in PAH. We observed an upregulation in both Gal-3 and alpha SMA expression in the monocrotaline (MCT) and Hypoxia PAH model, accompanied with intimal thickening. For more profound vascular remodeling and endothelial layer lesion in former model, we employed Gal-3 knockdown and overexpression lentivirus methodology to the MCT rats to determine the mechanisms underlying abnormal endothelial cell transition in PAH. PAH was evaluated according to right ventricular systolic pressure, right heart hypertrophy and pulmonary artery remodeling. A reduction in Gal-3 was protective against the development of PAH, while Gal-3 upregulation aggravated pulmonary vascular occlusion. In addition, Gal-3 deficiency suppressed pulmonary vascular cell proliferation and macrophage infiltration. Finally, we revealed that in endothelial cells treated with tumor necrosis factor alpha and hypoxia (representing an in vitro model of PAH), inhibition of Gal-3 by siRNA was able to abolish the associated upregulation of alpha SMA. These observations suggesting Gal-3 serves as a critical mediator in PAH by regulating EndoMT. Inhibition of Gal-3 may represent a novel therapeutic target for PAH treatment.

Galectin 3 endothelial-to-mesenchymal transition pulmonary arterial hypertension

SCI

英语

其他

national Natural Science Foundation of China[81570050]

Geriatrics & Gerontology

Geriatrics & Gerontology

WOS:000478762200005

INT SOC AGING & DISEASE

Web of Science

1.Cent S Univ, Xiangya Hosp, Dept Cardiol, Changsha, Hunan, Peoples R China
2.Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fu Wai Hosp, State Key Lab Cardiovasc Dis, Beijing, Peoples R China
3.Peking Union Med Coll, Beijing, Peoples R China
4.Imperial Coll London, Hammersmith Hosp, Div Expt Med, Ctr Pharmacol & Therapeut, London W12 0NN, England
5.Cent S Univ, Sch Pharmaceut Sci, Dept Pharmacol, Changsha, Hunan, Peoples R China
6.Jinan Univ, Southern Univ Sci & Technol, Clin Med Coll 2, Affiliated Hosp 1,Shenzhen Peoples Hosp,Dept Card, Guangzhou, Guangdong, Peoples R China

Li, Tangzhiming,Zha, Lihuang,Luo, Hui,et al. Galectin-3 Mediates Endothelial-to-Mesenchymal Transition in Pulmonary Arterial Hypertension[J]. Aging and Disease,2019,10(4):731-745.

Li, Tangzhiming.,Zha, Lihuang.,Luo, Hui.,Li, Suqi.,Zhao, Lin.,...&Yu, Zaixin.(2019).Galectin-3 Mediates Endothelial-to-Mesenchymal Transition in Pulmonary Arterial Hypertension.Aging and Disease,10(4),731-745.

Li, Tangzhiming,et al."Galectin-3 Mediates Endothelial-to-Mesenchymal Transition in Pulmonary Arterial Hypertension".Aging and Disease 10.4(2019):731-745.