ArticleAmerican journal of physiology. Lung cellular and molecular physiology2009
Transforming growth factor-beta1 causes pulmonary microvascular endothelial cell apoptosis via ALK5.
Article in American journal of physiology. Lung cellular and molecular physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Transmembrane Protein 100 Expression on Endothelial Cells Vascularizing Thrombi in Chronic Thromboembolic Pulmonary Hypertension Modulates TGFβ1-ALK1 Signaling During Angiogenesis.Pulmonary circulation · 2026Article
- PFKFB3 Promotes Myofibroblast Differentiation and Cardiac Fibrosis Through its Intra- and Extra- Cellular Roles.Journal of cardiovascular translational research · 2025Article
- 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
- Myofibroblasts reduce angiogenesis and vasculogenesis in a vascularized microphysiological model of lung fibrosis.bioRxiv : the preprint server for biology · 2025Article
- Commercial human pulmonary artery endothelial cells have in-vitro behavior that varies by sex.Pulmonary circulation · 2022Article
- Molecular pathogenesis and treatment of cavernous nerve injury-induced erectile dysfunction: A narrative review.Frontiers in physiology · 2022Review
- Synthesis of Reactive Sulfur Species in Cultured Vascular Endothelial Cells after Exposure to TGF-βInternational journal of molecular sciences · 2021Article
- Culture of pulmonary artery endothelial cells from pulmonary artery catheter balloon tips: considerations for use in pulmonary vascular disease.The European respiratory journal · 2020Article
- Reactive Oxygen Species-Dependent Calpain Activation Contributes to Airway and Pulmonary Vascular Remodeling in Chronic Obstructive Pulmonary Disease.Antioxidants & redox signaling · 2019Article
- TGF-β1 in Vascular Wall Pathology: Unraveling Chronic Venous Insufficiency Pathophysiology.International journal of molecular sciences · 2017Review
- Capsaicin-induced CaAmerican journal of physiology. Lung cellular and molecular physiology · 2017Article
- BMP-7 induces apoptosis in human germinal center B cells and is influenced by TGF-β receptor type I ALK5.PloS one · 2017Article
- Smad-independent pathway involved in transforming growth factor β1-induced Nox4 expression and proliferation of endothelial cells.Naunyn-Schmiedeberg's archives of pharmacology · 2015Article
- Article
- Cigarette smoke-induced lung endothelial apoptosis and emphysema are associated with impairment of FAK and eIF2α.Microvascular research · 2014Article
- Nox4 and redox signaling mediate TGF-β-induced endothelial cell apoptosis and phenotypic switch.Cell death & disease · 2014Article
- Sustained adenosine exposure causes lung endothelial apoptosis: a possible contributor to cigarette smoke-induced endothelial apoptosis and lung injury.American journal of physiology. Lung cellular and molecular physiology · 2013Article
- Mesenchymal stem cells attenuate vascular remodeling in monocrotaline-induced pulmonary hypertension rats.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2012Article
- Genetic disruption of protein kinase Cδ reduces endotoxin-induced lung injury.American journal of physiology. Lung cellular and molecular physiology · 2012Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We have previously shown that transforming growth factor (TGF)-beta1 protected against main pulmonary artery endothelial cell (PAEC) apoptosis induced by serum deprivation and VEGF receptor blockade through a mechanism associated with ALK5-mediated Bcl-2 upregulation. In the current study, we investigated the effect of TGF-beta1 on pulmonary microvascular endothelial cell (PMVEC) apoptosis. We found that, in contrast to the results seen in conduit PAEC, TGF-beta1 caused apoptosis of PMVEC, an effect that was also dependent on ALK5 activity. We noted that non-SMAD signaling pathways did not play a role in TGF-beta1-induced apoptosis. Both SMAD2 and SMAD1/5 were activated upon exposure to TGF-beta1. TGF-beta1-induced activation of SMAD2, but not SMAD1/5, was abolished by ALK5 inhibition, an effect that associated with prevention of TGF-beta1-induced apoptosis. These results suggest that SMAD2 is important in TGF-beta1-induced apoptosis of PMVEC. While caspase-12 activity was not altered, caspase-8 was activated by TGF-beta1, an effect that correlated with a reduction of cFLIP protein levels. Additionally, TGF-beta1 decreased Bcl-2 protein levels and induced cytochrome c cytosolic redistribution. These results suggest that TGF-beta1 caused apoptosis of PMVEC likely through both caspase-8-dependent extrinsic pathway and mitochondria-mediated intrinsic pathway. We noted that inhibition of ALK5 attenuated serum deprivation-induced apoptosis, an effect that correlated with increased expression and activation of CREB and its potential target genes, Bcl-2 and cFLIP. These results suggest that CREB may be important in mediating apoptosis resistance of PMVEC upon ALK5 inhibition perhaps through upregulation of Bcl-2 and cFLIP. Finally, we noted that SMAD1/5 were activated upon ALK5 inhibition in the presence of low levels of TGF-beta1, an effect associated with enhanced endothelial proliferation. We speculate that imbalance of ALK1 and ALK5 may contribute to the development of pulmonary artery hypertension.
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