ArticleAmerican journal of physiology. Lung cellular and molecular physiology2017
Transglutaminase 2 in pulmonary and cardiac tissue remodeling in experimental pulmonary hypertension.
Article in American journal of physiology. Lung cellular and molecular physiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 44 citations in OpenAlex.
- Beyond neurotransmission: the roles of serotonylation in physiological and pathological processes.Cellular & molecular biology letters · 2026Review
- Impact of TRP Channels on Extracellular Matrix Remodeling: Focus on TRPV4 and Collagen.International journal of molecular sciences · 2024Review
- Lung-specific interleukin 6 mediated transglutaminase 2 activation and cardiopulmonary fibrogenesis.Frontiers in immunology · 2024Article
- Article
- Article
- Cystamine reduces vascular stiffness in Western diet-fed female mice.American journal of physiology. Heart and circulatory physiology · 2022Article
- Article
- Increased Transglutaminase 2 Expression and Activity in Rodent Models of Obesity/Metabolic Syndrome and Aging.Frontiers in physiology · 2020Article
- Glycolysis regulated transglutaminase 2 activation in cardiopulmonary fibrogenic remodeling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Article
- CrossTalk proposal: The mouse SuHx model is a good model of pulmonary arterial hypertension.The Journal of physiology · 2019Article
- CrossTalk opposing view: The mouse SuHx model is not a good model of pulmonary arterial hypertension.The Journal of physiology · 2019Article
- Rebuttal from Sally H. Vitali.The Journal of physiology · 2019Article
- Serotonylation: Serotonin Signaling and Epigenetics.Frontiers in molecular neuroscience · 2019Review
- Switching-Off Adora2b in Vascular Smooth Muscle Cells Halts the Development of Pulmonary Hypertension.Frontiers in physiology · 2018Article
- Mechanobiological Feedback in Pulmonary Vascular Disease.Frontiers in physiology · 2018Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Tissue matrix remodeling and fibrosis leading to loss of pulmonary arterial and right ventricular compliance are important features of both experimental and clinical pulmonary hypertension (PH). We have previously reported that transglutaminase 2 (TG2) is involved in PH development while others have shown it to be a cross-linking enzyme that participates in remodeling of extracellular matrix in fibrotic diseases in general. In the present studies, we used a mouse model of experimental PH (Sugen 5416 and hypoxia; SuHypoxia) and cultured primary human cardiac and pulmonary artery adventitial fibroblasts to evaluate the relationship of TG2 to the processes of fibrosis, protein cross-linking, extracellular matrix collagen accumulation, and fibroblast-to-myofibroblast transformation. We report here that TG2 expression and activity as measured by serotonylated fibronectin and protein cross-linking activity along with fibrogenic markers are significantly elevated in lungs and right ventricles of SuHypoxic mice with PH. Similarly, TG2 expression and activity, protein cross-linking activity, and fibrogenic markers are significantly increased in cultured cardiac and pulmonary artery adventitial fibroblasts in response to hypoxia exposure. Pharmacological inhibition of TG2 activity with ERW1041E significantly reduced hypoxia-induced cross-linking activity and synthesis of collagen 1 and α-smooth muscle actin in both the in vivo and in vitro studies. TG2 short interfering RNA had a similar effect in vitro. Our results suggest that TG2 plays an important role in hypoxia-induced pulmonary and right ventricular tissue matrix remodeling in the development of PH.
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