ArticleAmerican journal of physiology. Lung cellular and molecular physiology2008
Transforming growth factor-beta1 protects against pulmonary artery endothelial cell apoptosis via ALK5.
Article in American journal of physiology. Lung cellular and molecular physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Physiological shear stress suppresses apoptosis in human pulmonary microvascular endothelial cells.Physiological reports · 2025Article
- Flavonoids Regulate Inflammation and Oxidative Stress in Cancer.Molecules (Basel, Switzerland) · 2020Review
- Stable isotope metabolomics of pulmonary artery smooth muscle and endothelial cells in pulmonary hypertension and with TGF-beta treatment.Scientific reports · 2020Article
- Focus on Early Events: Pathogenesis of Pulmonary Arterial Hypertension Development.Antioxidants & redox signaling · 2019Review
- Injury-Induced Shedding of Extracellular Vesicles Depletes Endothelial Cells of Cav-1 (Caveolin-1) and Enables TGF-β (Transforming Growth Factor-β)-Dependent Pulmonary Arterial Hypertension.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- Pulmonary Endothelial Cell Apoptosis in Emphysema and Acute Lung Injury.Advances in anatomy, embryology, and cell biology · 2018Review
- TGF-β1 in Vascular Wall Pathology: Unraveling Chronic Venous Insufficiency Pathophysiology.International journal of molecular sciences · 2017Review
- Fisetin inhibits liver cancer growth in a mouse model: Relation to dopamine receptor.Oncology reports · 2017Article
- Signaling by TGF-betas in tubule cultures of adult rat testis.American journal of translational research · 2017Article
- Zoledronic acid suppresses transforming growth factor-β-induced fibrogenesis by human gingival fibroblasts.International journal of molecular medicine · 2016Article
- TGFβ signalling pathway regulates angiogenesis by endothelial cells, in an adipose-derived stromal cell/endothelial cell co-culture 3D gel model.Cell proliferation · 2015Article
- Nox4 and redox signaling mediate TGF-β-induced endothelial cell apoptosis and phenotypic switch.Cell death & disease · 2014Article
- Endoglin regulates the activation and quiescence of endothelium by participating in canonical and non-canonical TGF-β signaling pathways.Journal of cell science · 2013Article
- Article
- TGFB1 disrupts the angiogenic potential of microvascular endothelial cells of the corpus luteum.Journal of cell science · 2011Article
- Alterations in molecular chaperones and eIF2alpha during lung endothelial cell apoptosis.American journal of physiology. Lung cellular and molecular physiology · 2010Article
- Transforming growth factor-beta1 causes pulmonary microvascular endothelial cell apoptosis via ALK5.American journal of physiology. Lung cellular and molecular physiology · 2009Article
- TGF-beta is required for vascular barrier function, endothelial survival and homeostasis of the adult microvasculature.PloS one · 2009Article
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1 author at 1 institution in 1 country.
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Abstract
Transforming growth factor (TGF)-beta1 has been reported to cause endothelial cell apoptosis. However, conflicting data have also demonstrated that TGF-beta1 promotes endothelial cell survival. In this study, the effect of TGF-beta1 on apoptosis of cultured bovine pulmonary artery endothelial cells (PAEC) induced by multiple stimuli was investigated. TGF-beta1 protected against apoptosis of bovine PAEC induced by serum deprivation or the VEGF receptor inhibitor SU-5416, but not by UV light exposure or TNFalpha. Neither caspase-8 nor caspase-12 was activated by serum deprivation or the VEGF receptor blocker. However, blockade of VEGF receptors activated caspase-9, an effect that was abolished by TGF-beta1. Furthermore, serum deprivation and inhibition of VEGF receptors significantly decreased the protein level of Bcl-2, an effect that was also abrogated by TGF-beta1. In addition, the baseline level of Bcl-2 was enhanced by TGF-beta1 and reduced by inhibition of activin receptor-like kinase 5 (ALK5), a TGF-beta1 type I receptor. Furthermore, inhibition of ALK5 caused apoptosis of bovine PAEC. These results suggest that TGF-beta1 signaling is critical for maintenance of bovine PAEC survival. Finally, the protective effects of TGF-beta1 on bovine PAEC apoptosis and Bcl-2 reduction were abolished by ALK5 inhibition, but not by inhibition of non-SMAD signaling pathways. Also, TGF-beta1 activated SMAD2 and SMAD1/5, an effect that was abolished by ALK5 inhibition. The results of this study suggest that TGF-beta1 protects against bovine PAEC apoptosis, possibly through ALK5-mediated Bcl-2 induction and subsequent inhibition of the mitochondria-mediated intrinsic pathway of apoptosis. Understanding the mechanism by which TGF-beta1 promotes endothelial cell survival may provide a better treatment for apoptosis-dependent vascular diseases, such as emphysema.
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