{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe urotensin‐II (UII) system, encompassing UII and its receptor (UT), is emerging as a multifaceted regulator of both central and peripheral functions. In the central nervous system, UII modulates behavior and neuroendocrine secretions – with intracerebroventricular injections in mice inducing dose‐dependent anxiogenic and depressant‐like effects, along with alterations in feeding and locomotor activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the vasculature, the UII/UT system is implicated in atherosclerotic processes and vascular remodeling. Experimental studies have demonstrated that deletion of the UII gene or blockade of its receptor can ameliorate atherosclerosis, while upregulation of UII is associated with exacerbated diabetic and non‐diabetic atherosclerotic changes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe inflammatory and immune‐related roles of the UII/UT system have also been well documented. In models of acute liver failure and sepsis, enhanced UII/UT expression correlates with increases in proinflammatory cytokines and activation of signaling pathways such as NF‐κB, and administration of UII receptor antagonists can significantly reduce liver injury and lung damage."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, the UII system plays a crucial role in neuromuscular and metabolic regulation. UII and its related peptide are expressed in motoneurons and at neuromuscular junctions, suggesting a role in motor control, while in peripheral tissues, particularly skeletal muscle, UII upregulation is linked to insulin resistance, impaired glucose uptake, and muscle atrophy via mechanisms involving autophagy and the ubiquitin-proteasome pathway."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "12"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, studies in models of sepsis and systemic sclerosis reveal that pharmacological antagonism of UII receptors can mitigate inflammatory lung injury and reduce profibrotic factors, underscoring the therapeutic potential of targeting this system in diverse pathological conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nCollectively, these findings suggest that the UII/UT system is a key mediator across multiple systems—from modulating central behavioral responses and vascular pathology to influencing inflammatory cascades and skeletal muscle homeostasis. Although the abstracts provided do not specifically address TRGC1, the insights into UII’s diverse functions may offer parallels for future studies aiming to elucidate the role of related regulatory or receptor genes in similar pathophysiological contexts.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jean-Claude Do-Rego, David Chatenet, Marie-Hélène Orta, et al. 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