PGF2α-FP Receptor Ameliorates Senescence of VSMCs in Vascular Remodeling by Src/PAI-1 Signal Pathway.

Abstract

Senescence in vascular smooth muscle cells (VSMCs) is involved in vascular remodeling of aged mice. ProstaglandinF2α- (PGF2α-) FP receptor plays a critical role in cardiovascular diseases (CVDs), hypertension, and cardiac fibrosis. However, its role in senescence-induced arteriosclerosis is yet to be fully elucidated. In this study, we found that FP receptor expression increased in aged mouse aortas and senescence VSMCs. FP receptor gene silencing can ameliorate vascular aging and inhibit oxidative stress, thereby reducing the expression of PAI-1, inhibiting the activation of MMPs, and ultimately improving the excessive deposition of ECM and delaying the process of vascular fibrosis. FP receptor could promote VSMC senescence by upregulated Src/PAI-1 signal pathway, and inhibited FP receptor/Src/PAI-1 pathway could ameliorate VSMCs aging in vitro, evidenced by the decrease of senescence-related proteins P16, P21, P53, and GLB1 expressions. These results suggested that FP receptor is a promoter of vascular aging, by inducing cellular aging, oxidative stress, and vascular remodeling via Src and PAI-1 upregulation.

• Authors: Bo-Ang Hu, Wen-Wen Sai, Jun Yuan, Hong-Tao Lan, Jia Qi, Di Wang, Wei Zhang, Zhi-Hao Wang, Ming Zhong, Yuan-Yuan Shang
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2022 Pg. 2908261 ( 2022) ISSN: 1942-0994 [Electronic] United States
• PMID: 35126810 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Bo-ang Hu et al.

Chemical References

• Plasminogen Activator Inhibitor 1
• RNA, Small Interfering
• Receptors, Prostaglandin
• Tumor Suppressor Protein p53
• prostaglandin F2alpha receptor
• Nitric Oxide
• Collagen
• src-Family Kinases

Topics

• Animals
• Aorta (metabolism, pathology)
• Cellular Senescence
• Collagen (genetics, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Muscle, Smooth, Vascular (cytology, metabolism)
• Nitric Oxide (metabolism)
• Oxidative Stress (genetics)
• Plasminogen Activator Inhibitor 1 (genetics, metabolism)
• RNA Interference
• RNA, Small Interfering (metabolism)
• Rats
• Receptors, Prostaglandin (antagonists & inhibitors, genetics, metabolism)
• Signal Transduction
• Tumor Suppressor Protein p53 (genetics, metabolism)
• Up-Regulation
• Vascular Remodeling
• src-Family Kinases (genetics, metabolism)