Restoration of miR-328a-5p function curtails hypoxic pulmonary hypertension through a mechanism involving PIN1/GSK3ß/ß-catenin axis.
Int Immunopharmacol
; 123: 110599, 2023 Oct.
Article
in En
| MEDLINE
| ID: mdl-37567011
ABSTRACT
Recent evidence has highlighted the involvement of microRNAs (miRs) in hypoxic pulmonary hypertension (PH), which can be induced under hypoxic conditions. We intend to explore whether the miR-328a-5p/PIN1 axis affects hypoxic PH by regulating the GSK3ß/ß-catenin signaling pathway. The GEO database was retrieved to single out key miRs affecting hypoxic PH. It was observed that downregulation of miR-328a-5p occurred in hypoxia-induced PH samples. The binding affinity between miR-328a-5p to PIN1 was predicted by a bioinformatics tool and verified using a dual luciferase reporter gene assay. Rat primary pulmonary artery smooth muscle cells (PASMCs) were exposed to hypoxia for in vitro cell experiments. miR-328a-5p could target and downregulate PIN1 expression, leading to suppressed GSK3ß/ß-catenin activation. In addition, GSK3ß/ß-catenin inactivation curtailed hypoxia-induced vascular inflammatory responses and proliferation and migration in PASMCs in vitro. A hypoxic PH model was established in SD rats to observe the effects of miR-328a-5p on hemodynamic parameters and right heart remodeling. It was demonstrated in vivo that miR-328a-5p downregulated PIN1 expression to suppress GSK3ß/ß-catenin signaling, thereby reducing the vascular inflammatory response and alleviating disease progression in hypoxia-induced PH rats. The evidence provided by our study highlighted the involvement of miR-328a-5p in the translational suppression of PIN1 and the blockade of the GSK3ß/ß-catenin signaling pathway, resulting in attenuation of hypoxic PH progression.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
MicroRNAs
/
Hypertension, Pulmonary
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Int Immunopharmacol
Journal subject:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Year:
2023
Document type:
Article