{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUrotensin II, the peptide encoded by the UTS2 gene, is a highly potent vasoactive molecule that plays a central role in cardiovascular regulation. It exerts powerful vasoconstrictor—and in some vascular beds, vasodilator—effects and has been implicated in modulating cardiac contractility, smooth muscle proliferation, and vascular remodeling. Elevated Urotensin II levels and increased UTS2 gene expression have been observed in patients with congestive heart failure, hypertension, and atherosclerosis, suggesting that this peptide may participate both in maladaptive remodeling and in compensatory cardiostimulatory responses. In addition, activation of its G protein–coupled receptor elicits diverse intracellular signaling cascades—including NADPH oxidase activation, protein kinase C, and Rho kinase pathways—that ultimately influence endothelial cell survival and smooth muscle cell proliferation, thereby impacting vascular homeostasis and repair."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "18"}]}, {"type": "t", "text": "\n \n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic and metabolic studies further indicate that variations in the UTS2 gene contribute to inter‐individual differences in susceptibility to metabolic derangements and cardiovascular risk factors. Several single nucleotide polymorphisms in UTS2 have been associated with type 2 diabetes mellitus, insulin resistance, and even diabetic retinopathy, thereby suggesting a diabetogenic role for Urotensin II. In subjects with metabolic syndrome and related conditions—including end‐stage renal disease where Urotensin II levels correlate inversely with adverse cardiovascular outcomes—the peptide appears to adversely influence insulin secretion and sensitivity. Collectively, these data point to a link between UTS2 genetic variability and the interplay between metabolic dysregulation and vascular pathology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "29"}]}, {"type": "t", "text": "\n \n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its well‐established cardiovascular and metabolic roles, Urotensin II also appears to influence a range of non‐cardiovascular pathophysiological processes. Comparative studies with related peptides have highlighted differential central as well as peripheral processing of its precursor, with immunohistochemical evidence showing prominent expression in motoneurons of the human spinal cord. Moreover, Urotensin II contributes to inflammatory signaling by modulating expression of adhesion molecules and cytokines such as interleukin‑8 in endothelial cells, and it has been implicated in angiogenic responses, particularly in settings of tissue injury and tumorigenesis. In the liver and adrenal tissues, for example, upregulation of Urotensin II and its receptor has been associated with cell proliferation and fibrosis, underscoring its potential as a therapeutic target in hepato‐cellular carcinoma, portal hypertension, and even rheumatic valve disease. Additionally, studies assessing its clearance and secretion suggest that dysregulation of Urotensin II homeostasis may underlie aspects of cardiovascular and renal dysfunction."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "30", "end_ref": "41"}]}, {"type": "t", "text": ""}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Thomas Dschietzig, Cornelia Bartsch, Rainer Pregla, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Elevated plasma levels of human urotensin-II immunoreactivity in congestive heart failure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Heart Circ Physiol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpheart.00217.2003"}], "href": "https://doi.org/10.1152/ajpheart.00217.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12791592"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12791592"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Melissa Lim, Suzy Honisett, Christopher D Sparkes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential effect of urotensin II on vascular tone in normal subjects and patients with chronic heart failure."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.CIR.0000121326.69153.98"}], "href": "https://doi.org/10.1161/01.CIR.0000121326.69153.98"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15007012"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15007012"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Bernard M Y Cheung, Raymond Leung, Yu Bun Man, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plasma concentration of urotensin II is raised in hypertension."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hypertens (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/01.hjh.0000125452.28861.f1"}], "href": "https://doi.org/10.1097/01.hjh.0000125452.28861.f1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15201550"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15201550"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Nicolas Bousette, Lisa Patel, Stephen A Douglas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased expression of urotensin II and its cognate receptor GPR14 in atherosclerotic lesions of the human aorta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Atherosclerosis (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.atherosclerosis.2004.03.023"}], "href": "https://doi.org/10.1016/j.atherosclerosis.2004.03.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15306183"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15306183"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Talija Djordjevic, Rachida S BelAiba, Steve Bonello, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human urotensin II is a novel activator of NADPH oxidase in human pulmonary artery smooth muscle cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.ATV.0000154279.98244.eb"}], "href": "https://doi.org/10.1161/01.ATV.0000154279.98244.eb"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15618545"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15618545"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "R J Balment, W Song, N Ashton "}, {"type": "b", "children": [{"type": "t", "text": "Urotensin II: ancient hormone with new functions in vertebrate body fluid regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann N Y Acad Sci (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1196/annals.1327.007"}], "href": "https://doi.org/10.1196/annals.1327.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15891007"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15891007"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Takuya Watanabe, Toshiaki Suguro, Tomoko Kanome, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human urotensin II accelerates foam cell formation in human monocyte-derived macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hypertension (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.HYP.0000184226.99196.b5"}], "href": "https://doi.org/10.1161/01.HYP.0000184226.99196.b5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16172428"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16172428"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Libin Shi, Wenghui Ding, Dayuan Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proliferation and anti-apoptotic effects of human urotensin II on human endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Atherosclerosis (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.atherosclerosis.2005.10.044"}], "href": "https://doi.org/10.1016/j.atherosclerosis.2005.10.044"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16343502"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16343502"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Yi-Chun Zhu, Yi-Zhun Zhu, Philip Keith Moore "}, {"type": "b", "children": [{"type": "t", "text": "The role of urotensin II in cardiovascular and renal physiology and diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Pharmacol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.bjp.0706800"}], "href": "https://doi.org/10.1038/sj.bjp.0706800"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16783414"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16783414"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "N Ashton "}, {"type": "b", "children": [{"type": "t", "text": "Renal and vascular actions of urotensin II."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Kidney Int (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.ki.5001621"}], "href": "https://doi.org/10.1038/sj.ki.5001621"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16807543"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16807543"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "L Yi, Y H Gu, X L Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of ACE, ACE2 and UTS2 polymorphisms with essential hypertension in Han and Dongxiang populations from north-western China."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Int Med Res (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1177/147323000603400306"}], "href": "https://doi.org/10.1177/147323000603400306"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16866021"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16866021"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Ryo Morimoto, Fumitoshi Satoh, Osamu Murakami, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Immunolocalization of urotensin II and its receptor in human adrenal tumors and attached non-neoplastic adrenal tissues."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Peptides (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.peptides.2007.06.025"}], "href": "https://doi.org/10.1016/j.peptides.2007.06.025"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17686550"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17686550"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "P Cirillo, S De Rosa, M Pacileo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human urotensin II induces tissue factor and cellular adhesion molecules expression in human coronary endothelial cells: an emerging role for urotensin II in cardiovascular disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1538-7836.2008.02923.x"}], "href": "https://doi.org/10.1111/j.1538-7836.2008.02923.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18284603"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18284603"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "W Lu, A E S Abdel-Razik, N Ashton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Urotensin II: lessons from comparative studies for general endocrinology."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gen Comp Endocrinol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ygcen.2008.03.010"}], "href": "https://doi.org/10.1016/j.ygcen.2008.03.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18440535"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18440535"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "E Zomer, I de Ridder, A Kompa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effect of urotensin II on skin microvessel tone in diabetic patients without heart failure or essential hypertension."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Pharmacol Physiol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1440-1681.2008.04960.x"}], "href": "https://doi.org/10.1111/j.1440-1681.2008.04960.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18505448"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18505448"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Luisa Giuliani, Livia Lenzini, Michele Antonello, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and functional role of urotensin-II and its receptor in the adrenal cortex and medulla: novel insights for the pathophysiology of primary aldosteronism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2008-1131"}], "href": "https://doi.org/10.1210/jc.2008-1131"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19001524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19001524"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "San Bao Chai, Xue Min Li, Yong Zheng Pang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased plasma levels of endothelin-1 and urotensin-II in patients with coronary heart disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Heart Vessels (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00380-009-1178-6"}], "href": "https://doi.org/10.1007/s00380-009-1178-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20339975"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20339975"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Fang Zhu, Linong Ji, Bin Luo "}, {"type": "b", "children": [{"type": "t", "text": "[The role of urotensin II gene in the genetic susceptibility to type 2 diabetes in Chinese population]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zhonghua Yi Xue Za Zhi (2002)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12509909"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12509909"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Z Wenyi, S Suzuki, M Hirai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of urotensin II gene in genetic susceptibility to Type 2 diabetes mellitus in Japanese subjects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetologia (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00125-003-1145-1"}], "href": "https://doi.org/10.1007/s00125-003-1145-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12830381"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12830381"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Hong-xia Sun, Wei-nan Du, Jin Zuo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "[The association of two single nucleotide polymorphisms in PRKCZ and UTS2 respectively with type 2 diabetes in Han people of northern China]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zhongguo Yi Xue Ke Xue Yuan Xue Bao (2002)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12905622"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12905622"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Susumu Suzuki, Zong Wenyi, Masashi Hirai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variations at urotensin II and urotensin II receptor genes and risk of type 2 diabetes mellitus in Japanese."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Peptides (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.peptides.2004.03.030"}], "href": "https://doi.org/10.1016/j.peptides.2004.03.030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15476949"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15476949"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Kwok Leung Ong, Louisa Y F Wong, Yu Bun Man, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Haplotypes in the urotensin II gene and urotensin II receptor gene are associated with insulin resistance and impaired glucose tolerance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Peptides (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.peptides.2006.02.008"}], "href": "https://doi.org/10.1016/j.peptides.2006.02.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16597476"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16597476"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Damien Gruson, Michel F Rousseau, Jean-Marie Ketelslegers, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Raised plasma urotensin II in type 2 diabetes patients is associated with the metabolic syndrome phenotype."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Hypertens (Greenwich) (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1751-7176.2010.00336.x"}], "href": "https://doi.org/10.1111/j.1751-7176.2010.00336.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20695946"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20695946"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "María E Sáez, Tarik Smani, Reposo Ramírez-Lorca, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association analysis of urotensin II gene (UTS2) and flanking regions with biochemical parameters related to insulin resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0019327"}], "href": "https://doi.org/10.1371/journal.pone.0019327"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21559414"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21559414"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Seydi Okumus, Yusuf Ziya Igci, Tugba Taskin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between Thr21Met and Ser89Asn polymorphisms of the urotensin-II (UTS2) gene, diabetes mellitus, and diabetic retinopathy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Eye Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3109/02713683.2012.688181"}], "href": "https://doi.org/10.3109/02713683.2012.688181"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22587369"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22587369"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Hao Peng, Mingzhi Zhang, Xiaoqin Cai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between human urotensin II and essential hypertension--a 1:1 matched case-control study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0081764"}], "href": "https://doi.org/10.1371/journal.pone.0081764"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24339964"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24339964"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Wan-Yu He, Fei Wu, Xin-Xin Pang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Irisin is Associated with Urotensin II and Protein Energy Wasting in Hemodialysis Patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Kidney Blood Press Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000443412"}], "href": "https://doi.org/10.1159/000443412"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26870964"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26870964"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Eray Metin Guler, Mustafa Gokce, Ahmet Bacaksiz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Urotensin-II, oxidative stress, and inflammation increase in hypertensive and resistant hypertensive patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Hypertens (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/10641963.2020.1847128"}], "href": "https://doi.org/10.1080/10641963.2020.1847128"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33172302"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33172302"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Glenn R Valdez, Koki Inoue, George F Koob, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human urocortin II: mild locomotor suppressive and delayed anxiolytic-like effects of a novel corticotropin-releasing factor related peptide."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Res (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0006-8993(02)02707-5"}], "href": "https://doi.org/10.1016/s0006-8993(02"}, {"type": "t", "text": "02707-5) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12088848"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12088848"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Nicolas Chartrel, Jérôme Leprince, Cynthia Dujardin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biochemical characterization and immunohistochemical localization of urotensin II in the human brainstem and spinal cord."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurochem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1471-4159.2004.02698.x"}], "href": "https://doi.org/10.1111/j.1471-4159.2004.02698.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15379892"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15379892"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Giovanna Albertin, Diego Guidolin, Elisa Sorato, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pro-angiogenic activity of Urotensin-II on different human vascular endothelial cell populations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Regul Pept (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.regpep.2009.04.006"}], "href": "https://doi.org/10.1016/j.regpep.2009.04.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19362580"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19362580"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Yen-Hsing Chen, Timothy G Yandle, A Mark Richards, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Urotensin II immunoreactivity in the human circulation: evidence for widespread tissue release."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1373/clinchem.2009.131748"}], "href": "https://doi.org/10.1373/clinchem.2009.131748"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19797715"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19797715"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Diangang Liu, Jing Chen, Jin Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased expression of urotensin II and GPR14 in patients with cirrhosis and portal hypertension."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Med (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijmm_00000413"}], "href": "https://doi.org/10.3892/ijmm_00000413"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20428787"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20428787"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Yavuz Pehlivan, Bulent Gogebakan, Serdar Oztuzcu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association between Thr21Met and Ser89Asn polymorphisms of the urotensin II gene and systemic sclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Rheumatol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3899/jrheum.110509"}], "href": "https://doi.org/10.3899/jrheum.110509"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22045841"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22045841"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Chung-Yi Lee, Yi-Tin Tsai, Shih-Hurng Loh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Urotensin II induces interleukin 8 expression in human umbilical vein endothelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0090278"}], "href": "https://doi.org/10.1371/journal.pone.0090278"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24587311"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24587311"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Hamood Al Kindi, Anouar Hafiane, Zhipeng You, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circulating levels of the vasoactive peptide urotensin II in patients with acute coronary syndrome and stable coronary artery disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Peptides (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.peptides.2014.03.004"}], "href": "https://doi.org/10.1016/j.peptides.2014.03.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24642358"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24642358"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Yen-Ling Chen, Yi-Ting Tsai, Chung-Yi Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Urotensin II inhibits doxorubicin-induced human umbilical vein endothelial cell death by modulating ATF expression and via the ERK and Akt pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0106812"}], "href": "https://doi.org/10.1371/journal.pone.0106812"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25268131"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25268131"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Xiao-Tong Yu, Peng-Yan Wang, Zheng-Ming Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Up-regulation of urotensin II and its receptor contributes to human hepatocellular carcinoma growth via activation of the PKC, ERK1/2, and p38 MAPK signaling pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Molecules (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/molecules191220768"}], "href": "https://doi.org/10.3390/molecules191220768"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25514221"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25514221"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "C Lecointre, L Desrues, J E Joubert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Signaling switch of the urotensin II vasosactive peptide GPCR: prototypic chemotaxic mechanism in glioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2014.433"}], "href": "https://doi.org/10.1038/onc.2014.433"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25597409"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25597409"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "XiaoTong Yu, PengYan Wang, ZhengMing Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Urotensin-II-Mediated Reactive Oxygen Species Generation via NADPH Oxidase Pathway Contributes to Hepatic Oval Cell Proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0144433"}], "href": "https://doi.org/10.1371/journal.pone.0144433"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26658815"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26658815"}]}]}]}