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Aquaporin 1 confers apoptosis resistance in pulmonary arterial smooth muscle cells from the SU5416 hypoxia rat model.
- Source :
-
Physiological reports [Physiol Rep] 2024 Aug; Vol. 12 (16), pp. e16156. - Publication Year :
- 2024
-
Abstract
- Pulmonary hypertension (PH) arises from increased pulmonary vascular resistance due to contraction and remodeling of the pulmonary arteries. The structural changes include thickening of the smooth muscle layer from increased proliferation and resistance to apoptosis. The mechanisms underlying apoptosis resistance in PH are not fully understood. In cancer cells, high expression of aquaporin 1 (AQP1), a water channel, is associated with apoptosis resistance. We showed AQP1 protein was expressed in pulmonary arterial smooth muscle cells (PASMCs) and upregulated in preclinical PH models. In this study, we used PASMCs isolated from control male rats and the SU5416 plus hypoxia (SuHx) model to test the role of AQP1 in modulating susceptibility to apoptosis. We found the elevated level of AQP1 in PASMCs from SuHx rats was necessary for resistance to apoptosis and that apoptosis resistance could be conferred by increasing AQP1 in control PASMCs. In exploring the downstream pathways involved, we found AQP1 levels influence the expression of Bcl-2, with enhanced AQP1 levels corresponding to increased Bcl-2 expression, reducing the ratio of BAX to Bcl-2, consistent with apoptosis resistance. These results provide a mechanism by which AQP1 can regulate PASMC fate.<br /> (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)
- Subjects :
- Animals
Male
Rats
Rats, Sprague-Dawley
Hypertension, Pulmonary metabolism
Hypertension, Pulmonary pathology
Cells, Cultured
Proto-Oncogene Proteins c-bcl-2 metabolism
Proto-Oncogene Proteins c-bcl-2 genetics
Disease Models, Animal
Aquaporin 1 metabolism
Aquaporin 1 genetics
Apoptosis
Pulmonary Artery metabolism
Pulmonary Artery pathology
Pulmonary Artery cytology
Myocytes, Smooth Muscle metabolism
Myocytes, Smooth Muscle pathology
Muscle, Smooth, Vascular metabolism
Muscle, Smooth, Vascular pathology
Muscle, Smooth, Vascular cytology
Pyrroles pharmacology
Indoles pharmacology
Hypoxia metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2051-817X
- Volume :
- 12
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Physiological reports
- Publication Type :
- Academic Journal
- Accession number :
- 39175041
- Full Text :
- https://doi.org/10.14814/phy2.16156