ArticleCellular signalling2014
Tissue transglutaminase promotes serotonin-induced AKT signaling and mitogenesis in pulmonary vascular smooth muscle cells.
Article in Cellular signalling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 46 citations in OpenAlex.
- Cyclic stretch increases transglutaminase 2-mediated serotonylation of extracellular fibronectin in cultured optic nerve head astrocytes: a pilot study.Matrix biology plus · 2026Article
- Beyond neurotransmission: the roles of serotonylation in physiological and pathological processes.Cellular & molecular biology letters · 2026Review
- Role of Serotonin on Gene Expression and Physiology in Human Cytotrophoblasts and Placenta.Endocrinology · 2025Article
- CKB Promotes Mitochondrial ATP Production by Suppressing Permeability Transition Pore.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Role of Serotonylation and SERT Posttranslational Modifications in Alzheimer's Disease Pathogenesis.Aging and disease · 2024Review
- Transglutaminase 2 regulates endothelial cell calcification via IL-6-mediated autophagy.Frontiers in pharmacology · 2024Article
- Vascular smooth muscle ROCK1 contributes to hypoxia-induced pulmonary hypertension development in mice.Biochemical and biophysical research communications · 2022Article
- The Latest in Animal Models of Pulmonary Hypertension and Right Ventricular Failure.Circulation research · 2022Review
- A trial design to maximize knowledge of the effects of rodatristat ethyl in the treatment of pulmonary arterial hypertension (ELEVATE 2).Pulmonary circulation · 2022Article
- Cystamine reduces vascular stiffness in Western diet-fed female mice.American journal of physiology. Heart and circulatory physiology · 2022Article
- Serotonin: an overlooked regulator of endocytosis and endosomal sorting?Biology open · 2022Article
- mTOR Signaling in Pulmonary Vascular Disease: Pathogenic Role and Therapeutic Target.International journal of molecular sciences · 2021Review
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Direct Delivery of MicroRNA96 to the Lungs Reduces Progression of Sugen/Hypoxia-Induced Pulmonary Hypertension in the Rat.Molecular therapy. Nucleic acids · 2020Article
- Article
- Role of TG2-Mediated SERCA2 Serotonylation on Hypoxic Pulmonary Vein Remodeling.Frontiers in pharmacology · 2019Article
- Serotonylation: Serotonin Signaling and Epigenetics.Frontiers in molecular neuroscience · 2019Review
- Serotonin 2A receptor inhibition protects against the development of pulmonary hypertension and pulmonary vascular remodeling in neonatal mice.American journal of physiology. Lung cellular and molecular physiology · 2018Article
- Serotonin is an endogenous regulator of intestinal CYP1A1 via AhR.Scientific reports · 2018Article
- Transglutaminase 2 in pulmonary and cardiac tissue remodeling in experimental pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Tissue transglutaminase 2 (TG2) is a multifunctional enzyme that cross-links proteins with monoamines such as serotonin (5-hydroxytryptamine, 5-HT) via a transglutamidation reaction, and is associated with pathophysiologic vascular responses. 5-HT is a mitogen for pulmonary artery smooth muscle cells (PASMCs) that has been linked to pulmonary vascular remodeling underlying pulmonary hypertension development. We previously reported that 5-HT-induced PASMC proliferation is inhibited by the TG2 inhibitor monodansylcadaverine (MDC); however, the mechanisms are poorly understood. In the present study we hypothesized that TG2 contributes to 5-HT-induced signaling pathways of PASMCs. Pre-treatment of bovine distal PASMCs with varying concentrations of the inhibitor MDC led to differential inhibition of 5-HT-stimulated AKT and ROCK activation, while p-P38 was unaffected. Concentration response studies showed significant inhibition of AKT activation at 50 μM MDC, along with inhibition of the AKT downstream targets mTOR, p-S6 kinase and p-S6. Furthermore, TG2 depletion by siRNA led to reduced 5-HT-induced AKT activation. Immunoprecipitation studies showed that 5-HT treatment led to increased levels of serotonylated AKT and increased TG2-AKT complex formations which were inhibited by MDC. Overexpression of TG2 point mutant cDNAs in PASMCs showed that the TG2 C277V transamidation mutant blunted 5-HT-induced AKT activation and 5-HT-induced PASMC mitogenesis. Finally, 5-HT-induced AKT activation was blunted in SERT genetic knock-out rat cells, but not in their wild-type counterpart. The SERT inhibitor imipramine similarly blocked AKT activation. These results indicate that TG2 contributes to 5-HT-induced distal PASMC proliferation via promotion of AKT signaling, likely via its serotonylation. Taken together, these results provide new insight into how TG2 may participate in vascular smooth muscle remodeling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.