Urotensin II: an inflammatory cytokine

Sun, Shihui; Liu, Liangming

doi:10.1530/joe-18-0505

Cited by 23 publications

(11 citation statements)

References 124 publications

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“…Cilia defects can trigger inflammation in the kidney and in the brain [34,35]. Moreover, Urotensin II signaling induces inflammation in many contexts [36], raising the interesting possibility that increased URP signaling from CSF-cNs could drive neuroinflammation in the rpgrip1l ∆/∆ zebrafish scoliosis model.…”

Section: Discussionmentioning

confidence: 99%

Loss of the Reissner Fiber and increased URP neuropeptide signaling underlie scoliosis in a zebrafish ciliopathy mutant

Vesque

Anselme

Pézeron³

et al. 2019

Preprint

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Cilia-driven movements of the cerebrospinal fluid (CSF) are involved in zebrafish axis straightness, both in embryos and juveniles [1,2]. In embryos, axis straightness requires ciliadependent assembly of the Reissner fiber (RF), a SCO-spondin polymer running down the brain and spinal cord CSF-filled cavities [3]. Reduced expression levels of the urp1 and urp2 genes encoding neuropeptides of the Urotensin II family in CSF-contacting neurons (CSF-cNs) also underlie embryonic ventral curvature of several cilia motility mutants [4]. Moreover, mutants for scospondin and uts2r3 (a Urotensin II peptide family receptor gene) develop scoliosis at juvenile stages [3,4]. However, whether RF maintenance and URP signaling are perturbed in juvenile scoliotic ciliary mutants and how these perturbations are linked to scoliosis is unknown. Here we produced mutants in the zebrafish ortholog of the human RPGRIP1L ciliopathy gene encoding a transition zone protein [5][6][7]. rpgrip1l -/zebrafish had normal embryogenesis and developed 3D spine torsions in juveniles. Cilia lining the CNS cavities were normal in rpgrip1l -/embryos but sparse and malformed in juveniles and adults.Hindbrain ventricle dilations were present at scoliosis onset, suggesting defects in CSF flow.Immunostaining showed a secondary loss of RF correlating with juvenile scoliosis.Surprisingly, transcriptome analysis of rgprip1l mutants at scoliosis onset uncovered increased levels of urp1 and urp2 expression. Overexpressing urp2 in foxj1-expressing cells triggered scoliosis in rpgrip1l heterozygotes. Thus, our results demonstrate that increased URP signaling drives scoliosis onset in a ciliopathy mutant. We propose that imbalanced levels of URP neuropeptides in CSF-cNs may be an initial trigger of scoliosis.

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Section: Discussionmentioning

confidence: 99%

Loss of the Reissner Fiber and increased URP neuropeptide signaling underlie scoliosis in a zebrafish ciliopathy mutant

Vesque

Anselme

Pézeron³

et al. 2019

Preprint

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“…14 In addition, U-II plays a key role in the onset and development of inflammatory diseases. 12 Previous studies have confirmed that high levels of U-II are found in the plaques of patients with atherosclerosis. 10,27 Proinflammatory cytokines such as interleukin (IL)-6, IL-1β, and interferon (IFN)-γ in atherosclerotic plaques, which are secreted by macrophages and lymphocytes, upregulate the expression of U-II, and the specific receptor UT which accelerates the formation of atherosclerotic plaques with autocrine/paracrine effects.…”

Section: Discussionmentioning

confidence: 86%

“…11 Moreover, U-II acts as an inflammatory cytokine, which may unify the molecular basis of the innate immune and inflammatory response. 12 Elevated plasma U-II levels were detected in adults with atherosclerosis, 10 hypertension, 13,14 and congestive heart failure, 15 although other studies reported inconsistent results. 16,17 In children, on the other hand, little information is available on U-II levels at an early stage of life.…”

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confidence: 99%

Birth Weight Standard Deviation Score is a Significant Determinant of Serum Urotensin-II Levels at Term-Equivalent Age in Preterm Infants

et al. 2020

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Objective Urotensin II (U-II) is a potent vasoconstrictor peptide, and increased U-II levels are associated with atherosclerosis and hypertension in adults. Low birth weight (LBW) infants have higher risks of such diseases in the future. A small number of nephrons is one of possible mechanism underlying these risks in LBW infants, while vascular elasticity and cardiac function might be another important factor. The objective of this study is to evaluate U-II levels in preterm LBW infants at an early stage of life and determine perinatal factors associated with U-II levels. Study Design The study population consisted of 57 preterm LBW infants (26 males and 31 females), including 49 appropriate for gestational age (AGA) and 8 small for gestational age (SGA) infants, born at a gestational age of ≤34 weeks with a mean birth weight of 1,589 g. Serum U-II levels were measured at term-equivalent age to evaluate perinatal factors related to serum U-II levels. Results Preterm SGA infants had significantly higher serum U-II levels than preterm AGA infants at term-equivalent age (p = 0.019). Serum U-II levels in preterm LBW infants at term-equivalent age were inversely correlated with birth weight standard deviation (SD) score in a simple regression analysis (r = − 0.395, p = 0,002) and the correlation was maintained in the multiple regression analysis. Conclusion Our results indicate that birth weight SD score might be associated with serum U-II levels in preterm LBW infants at term-equivalent age. Further studies are required to determine whether U-II levels at an early stage of life might influence the risk of atherosclerosis and hypertension. Key Points

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“…UT is broadly expressed in the central nervous, cardiovascular, and renal systems 10 . U‐II/UT signaling participates in various biological processes, such as cell proliferation, profibrotic activities, neurosecretory effects, insulin resistance, as well as carcinogenic and pro‐inflammatory effects 11 . Numerous studies have demonstrated that increased expression levels of U‐II and UT are implicated in various disorders, including essential hypertension, atherosclerosis, heart failure, diabetes mellitus, and renal diseases 12 .…”

Section: Introductionmentioning

confidence: 99%

Inhibition of U‐II/UT signaling ameliorates cystitis‐associated bladder hyperactivity by targeting the RhoA/Rho‐kinase pathway

Liu

Sun

et al. 2022

The Kaohsiung J of Med Scie

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Urotensin II (U‐II) and its receptor (UT) are involved in the pathogenesis of various diseases; however, their association with the development of cystitis has not been elucidated. The present study was designed to investigate the functional role of U‐II/UT signaling in cyclophosphamide (CYP)‐induced cystitis. A total of 60 female rats were randomly divided into the control and CYP‐treated groups. Intraperitoneal injection of CYP successfully induced cystitis in rats of the CYP‐treated group. The protein and mRNA expression levels of U‐II and UT were significantly enhanced in rat bladder tissues of the CYP‐treated group. Furthermore, the results of the immunofluorescence staining analysis demonstrated that CYP treatment apparently increased the expression levels of UT in the urothelium layer, detrusor smooth muscle, and bladder interstitial Cajal‐like cells. The selective antagonist of UT, SB657510 (10 μm), significantly suppressed the CYP‐induced increase in the spontaneous contractions of muscle strips and ameliorated the bladder hyperactivity of CYP‐treated rats. Moreover, CYP treatment significantly increased the protein expression levels of Ras homolog family member (Rho) A and Rho‐associated protein kinase 2 in rat bladder tissues. Following pretreatment with the Rho‐kinase inhibitor Y‐27632 (10 μm), the inhibitory effects of SB657510 (10 μm) on the spontaneous contractions of muscle strips were eliminated. In conclusion, the results of the present study suggested that activation of U‐II/UT signaling promoted the development of cystitis‐associated‐bladder hyperactivity by targeting the RhoA/Rho‐kinase pathway, indicating that the U‐II/UT signaling could serve as a novel target for the treatment of interstitial cystitis/bladder pain syndrome.

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Urotensin II: an inflammatory cytokine

Cited by 23 publications

References 124 publications

Loss of the Reissner Fiber and increased URP neuropeptide signaling underlie scoliosis in a zebrafish ciliopathy mutant

Loss of the Reissner Fiber and increased URP neuropeptide signaling underlie scoliosis in a zebrafish ciliopathy mutant

Birth Weight Standard Deviation Score is a Significant Determinant of Serum Urotensin-II Levels at Term-Equivalent Age in Preterm Infants

Inhibition of U‐II/UT signaling ameliorates cystitis‐associated bladder hyperactivity by targeting the RhoA/Rho‐kinase pathway

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