Lipocalin-2 induced LDHA expression promotes vascular remodelling in pulmonary hypertension.
Cell Prolif
; : e13717, 2024 Jul 18.
Article
en En
| MEDLINE
| ID: mdl-39021353
ABSTRACT
Aerobic glycolysis is involved in the pathogenesis of pulmonary hypertension (PH). The mechanisms by which glycolysis is increased and how it contributes to pulmonary vascular remodelling are not yet fully understood. In this study, we demonstrated that elevated lipocalin-2 (LCN2) in PH significantly enhances aerobic glycolysis in human pulmonary artery smooth muscle cells (PASMCs) by up-regulating LDHA expression. Knockout of Lcn2 or having heterozygous LDHA deficiency in mice significantly inhibits the progression of hypoxic PH. Our study reveals that LCN2 stimulates LDHA expression by activating Akt-HIF-1α signalling pathway. Inhibition of Akt or HIF-1α reduces LDHA expression and proliferation of PASMCs. Both Akt and HIF-1α play critical roles in the development of PH and are suppressed in the pulmonary vessels of hypoxic PH mice lacking LCN2. These findings shed light on the LCN2-Akt-HIF1α-LDHA axis in aerobic glycolysis in PH.
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1
Colección:
01-internacional
Banco de datos:
MEDLINE
Idioma:
En
Revista:
Cell Prolif
Año:
2024
Tipo del documento:
Article
País de afiliación:
China