{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUrocortin 2 (UCN2) is an endogenous peptide member of the corticotropin‐releasing factor family that predominantly signals via CRF receptor type 2. In cardiomyocytes, UCN2 and its related homologues exert potent cardioprotective effects by activating prosurvival cascades including the p42/44 MAPK and Akt pathways, thereby reducing apoptosis under stress conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In reproductive tissues, UCN2 is expressed in the myometrium and endometrium where it modulates smooth muscle contractility through sequential activation of protein kinase C, MAPK, and RhoA-associated kinase, and it regulates estradiol synthesis by upregulating aromatase expression in trophoblasts, suggesting a role in parturition and placental endocrine function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " When administered centrally, UCN2 markedly inhibits gastric emptying via a CRF receptor type‑2 mediated mechanism that involves sympathetic alpha‑adrenergic signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, its expression in gestational tissues further implicates UCN2 in the regulation of placental adrenocorticotropic hormone secretion and in modulating inflammatory processes during labor."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its reproductive and gastrointestinal functions, UCN2 plays complex roles in cardiovascular and inflammatory settings. Its expression is modulated by hypoxic stress in the placenta"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", and UCN2 is detectable in differentiated adipocytes where it may participate in the regulation of inflammatory cytokine production."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In joint tissues, particularly in osteoarthritis, UCN2 along with its family members contributes to the local cytokine milieu, thereby impacting inflammatory and destructive processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Its ability to modulate cytokine secretion extends to placental explants as well."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " At the molecular level, differences in post-translational processing of UCN2 between species have been characterized, providing insights into its bioactivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " In the vascular smooth muscle compartment, UCN2 has been shown to inhibit Akt phosphorylation and cell proliferation, a finding that associates it with the pathogenesis of abdominal aortic aneurysm"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ", and intriguingly, UCN2 also exhibits direct antimicrobial activity against bacterial and parasitic pathogens."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " Recombinant expression systems have been successfully employed to generate UCN2 for antibody production and further functional studies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nUCN2’s cardiovascular actions have emerged as particularly critical in disease contexts. Continuous infusion studies in animal models reveal that constitutive activation of CRF receptor type 2 by UCN2 aggravates cardiac dysfunction, with elevated plasma levels observed in patients with heart failure."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": " In hypertensive patients, UCN2 concentrations appear to interact with renin–angiotensin–aldosterone system blockade, suggesting that endogenous UCN2 may contribute to blood pressure regulation and vascular tone."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": " Collectively, these findings underscore the pleiotropic nature of UCN2 in orchestrating cardioprotective signaling, modulating smooth muscle contractility and inflammatory responses in reproductive and vascular tissues, and even exerting antimicrobial actions. Such multifunctionality positions UCN2 as an attractive therapeutic target in pathologies ranging from heart failure and vascular disorders to obstetric complications and inflammatory diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}, {"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "A Chanalaris, K M Lawrence, A Stephanou, et al. 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