Compensatory roles of Protein Related to DAN and Cerberus (PRDC) decrease in pulmonary arterial hypertension

He, Ting1,2; Zhang, Junzhi1,4; Qiao, Ting1,4; Zhang, Zhongjun1,4; Han, Hui3; Yang, Chao7; Chen, Yong5,6; Ruan, Yiwen2; Meng, Liukun3

2022

10.7150/ijbs.70247

International Journal of Biological Sciences   Impact Factor & Quartile

1449-2288

Bone morphogenetic protein (BMP) signaling is commonly suppressed in patients with pulmonary arterial hypertension (PAH), but the compensatory mechanism of BMP signaling suppression is incompletely elucidated. This study aimed to investigate the role of PRDC, an antagonist of BMPs, in PAH and the underlying mechanism. Human lungs were collected and rat PAH was induced (monocrotaline, 60 mg/kg). BMP cascade and PRDC were detected in lungs and distal pulmonary artery smooth muscle cells (dPASMCs). In vitro cell experiments and in vivo supplementation of PRDC in hypertensive rats were subsequently performed. PRDC and BMP cascade all decreased in human and rat hypertensive lungs. Cell experiments confirmed that BMP2/4 inhibited dPASMCs proliferation by increasing cell cycle inhibitors (p21, p27), prevented dPASMCs migration by down-regulating MMP2/9 and up-regulating TIMP1/2 expression, and promoted dPASMCs apoptosis by up-regulating Box, caspase3/9 and down-regulating Bcl-2 expression, as well as enhancing caspase3/7 activity, while, PRDC reversed the effects of BMP2/4 on dPASMCs proliferation, migration and apoptosis. In vivo trial found that PRDC supplementation deteriorated rat PAH in terms of pulmonary hemodynamics, vasculopathies and right ventricle hypertrophy. Taken together, compensatory decrease of PRDC in hypertensive lungs theoretically slow down the natural course of PAH, suggesting its therapeutic potential in PAH.

Pulmonary arterial hypertension pulmonary vascular remodeling bone morphogenetic protein monocrotaline PRDC

SCI

English

Others

National Natural Science Foundation of China["81700435","82070325"] ; Beijing Natural Science Foundation["7222138","7172182"] ; China Postdoctoral Science Foundation[2018M633284] ; Shenzhen Key Medical Discipline Construction Fund[SZXK044] ; Sanming Project of Medicine in Shenzhen[SZSM202011021]

Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics

Biochemistry & Molecular Biology ; Biology

WOS:000831182700011

IVYSPRING INT PUBL

Web of Science

1.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Anesthesiol, Shenzhen 518020, Peoples R China
2.Jinan Univ, Integrated Chinese & Western Med Postdoctoral Res, Guangzhou 510632, Peoples R China
3.Chinese Acad Med Sci & Peking Union Med Coll, Fuwai Hosp, Natl Ctr Cardiovasc Dis, State Key Lab Cardiovasc Dis, Beijing 100037, Peoples R China
4.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518020, Peoples R China
5.Shenzhen Univ, Gen Hosp, Dept Neurosurg, Shenzhen 518055, Peoples R China
6.Shenzhen Univ, Clin Med Acad, Dept Neurosurg, Shenzhen 518055, Peoples R China
7.Guangzhou Med Univ, Affiliated Hosp 1, Dept Organ Transplantat & Thorac Surg, Guangzhou 510120, Peoples R China

He, Ting,Zhang, Junzhi,Qiao, Ting,et al. Compensatory roles of Protein Related to DAN and Cerberus (PRDC) decrease in pulmonary arterial hypertension[J]. International Journal of Biological Sciences,2022,18(6).

He, Ting.,Zhang, Junzhi.,Qiao, Ting.,Zhang, Zhongjun.,Han, Hui.,...&Meng, Liukun.(2022).Compensatory roles of Protein Related to DAN and Cerberus (PRDC) decrease in pulmonary arterial hypertension.International Journal of Biological Sciences,18(6).

He, Ting,et al."Compensatory roles of Protein Related to DAN and Cerberus (PRDC) decrease in pulmonary arterial hypertension".International Journal of Biological Sciences 18.6(2022).