{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T11:53:47Z","timestamp":1782215627825,"version":"3.54.5"},"reference-count":43,"publisher":"IMR Press","issue":"5","license":[{"start":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T00:00:00Z","timestamp":1661472000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"General program of National Natural Science Foundation of China","award":["81874510"],"award-info":[{"award-number":["81874510"]}]},{"name":"University Student Innovation and Entrepreneurship Training Program Project of Hunan Province","award":["S202110541019"],"award-info":[{"award-number":["S202110541019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Integr. Neurosci."],"abstract":"<jats:p>Objective: This study aimed to conduct proteomic analysis of the sphincter in a neurogenic bladder caused by T10 spinal cord injury. The differentially expressed proteins (DEPs) of the sphincters (internal urethral sphincter) in the neurogenic bladders (NBs) of rats after complete transection of the T10 spinal cord segment were screened using tandem mass tag (TMT)-based quantitative labeling, and their biological information was analyzed. Methods: Twelve adult Sprague Dawley rats out of 40 were randomly assigned to the blank group (n = 12), while the remaining 28 were placed in the T10 spinal cord injury model via modified Hassan Shaker spinal cord transection; 12 of these rats were then randomly selected as the model group. The rats in both groups underwent urodynamics detection and hematoxylin and eosin (H&amp;E) staining. The proteins expressed in the bladder sphincter were detected using TMT-based quantitative proteomics. DEPs were defined as proteins with fold change &gt;1.5 or &lt;1\/1.5, p &lt; 0.05, and unique peptide \u22652. The DEPs were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis using KOBAS 3.0., and gene ontology functional annotation analysis was performed using the Cytoscape 3.7.1. BiNGO plug-in. The protein\u2013protein interaction network was then constructed using the interactive gene-retrieval tool STRING and Cytoscape software. Results: The leak-point pressure and maximum cystometric volume in the model group were significantly higher than those in the blank group (p &lt; 0.01), and H&amp;E staining showed continuous interruption of the bladder sphincter fibers in the model group. A total of 250 DEPs were screened in the bladder sphincter, 83 of which were up-regulated and 167 of which were down-regulated. KEGG analysis of the DEPs was used to screen 15 pathways, including metabolic pathways, extracellular matrix (ECM)-receptor interaction, adhesion spots, the phosphoinositide 3-kinase (PI3K)\/protein kinase B (Akt) signaling pathway, the cytochalasin signaling pathway, and the advanced glycation end-products (AGE)\/receptor for AGEs (RAGE) signaling pathway in diabetic complications and vascular smooth muscle contraction. Conclusions: It is of great significance to explore the pathological mechanism of non-inhibitory contraction of the bladder sphincter caused by spinal cord injury above the T10 segment from the perspective of ECM-receptor interaction, focal adhesion-activated PI3K\/Akt signaling pathway, and cell relaxation signaling pathways. Synaptic vesicle glycoprotein (Sv2A) involved in the release of neurotransmitters from synaptic vesicles, arrestin \u03b22 inhibitory proteins involved in \u03b1-adrenergic receptors and G-protein-coupled receptor internalization, and calmodulin and calmodulin binding protein involved in calcium-sensitive signaling pathways may be potential targets for developing new ways to treat bladder sphincter overactivity caused by T10 spinal cord injury.<\/jats:p>","DOI":"10.31083\/j.jin2105147","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T01:52:00Z","timestamp":1661737920000},"source":"Crossref","is-referenced-by-count":6,"title":["Proteomic Analysis of the Sphincter in a Neurogenic Bladder Caused by T10 Spinal Cord Injury"],"prefix":"10.31083","volume":"21","author":[{"given":"Qi-Rui","family":"Qu","sequence":"first","affiliation":[{"name":"College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medcine, 410208 Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Ya","family":"Tang","sequence":"first","affiliation":[{"name":"College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medcine, 410208 Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"Liu","sequence":"first","affiliation":[{"name":"College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medcine, 410208 Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ying","family":"Long","sequence":"first","affiliation":[{"name":"College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medcine, 410208 Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Wu","sequence":"first","affiliation":[{"name":"College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medcine, 410208 Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Xu","sequence":"first","affiliation":[{"name":"College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medcine, 410208 Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Qi","sequence":"first","affiliation":[{"name":"College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medcine, 410208 Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medcine, 410208 Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Ai","sequence":"first","affiliation":[{"name":"College of Acupuncture, Massage and Rehabilitation, Hunan University of Chinese Medcine, 410208 Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine, Chenzhou First People's Hospital, 423000 Chenzhou, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2022,8,26]]},"reference":[{"key":"ref1","unstructured":"Zhang Q, Zhao FF, Liu TP, Wang CK, He XW. Research Progress of Acupuncture in the Treatment of Neurogenic Bladder after Spinal Cord Injury in Recent Ten Years. Jiang Xi Jouranl of Traditional Chinese Medicine. 2021; 52: 74\u201377."},{"key":"ref2","unstructured":"Xiong ZS, Xu ZY. Urodynamic study and classification of the bladder after spinal cord injury. Modern Rehabilitation. 2000; 805\u2013807."},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Amarenco G, Sheikh Isma\u00ebl S, Chesnel C, Charlanes A, Le Breton F. Diagnosis and clinical evaluation of neurogenic bladder. European Journal of Physical and Rehabilitation Medicine. 2017; 53: 975\u2013980.","DOI":"10.23736\/S1973-9087.17.04992-9"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Mcbride AW. Pathphysio1gy of stress urinary incontinence. Journal of Pelvic Medicine and Surgery. 2004; 10: 1\u20137.","DOI":"10.1097\/01.spv.0000117312.27146.f8"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Ke QS, Kuo HC. Transurethral incision of the bladder neck to treat bladder neck dysfunction and voiding dysfunction in patients with high-level spinal cord injuries. Neurourology and Urodynamics. 2010; 29: 748\u2013752.","DOI":"10.1002\/nau.20812"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Krongrad A, Sotolongo JR Jr. Bladder neck dysynergia in spinal cord injury. American Journal of Physical Medicine & Rehabilitation. 1996; 75: 204\u2013207.","DOI":"10.1097\/00002060-199605000-00011"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Wyndaele JJ, Birch B, Borau A, Burks F, Castro-Diaz D, Chartier-Kastler E, et al. Surgical management of the neurogenic bladder after spinal cord injury. World Journal of Urology. 2018; 36: 1569\u20131576.","DOI":"10.1007\/s00345-018-2294-7"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Romo PGB, Smith CP, Cox A, Averbeck MA, Dowling C, Beckford C, et al. Non-surgical urologic management of neurogenic bladder after spinal cord injury. World Journal of Urology. 2018; 36: 1555\u20131568.","DOI":"10.1007\/s00345-018-2419-z"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Chen C, Hou J, Tanner JJ, Cheng J. Bioinformatics Methods for Mass Spectrometry-Based Proteomics Data Analysis. International Journal of Molecular Sciences. 2020; 21: 2873.","DOI":"10.3390\/ijms21082873"},{"key":"ref10","doi-asserted-by":"publisher","unstructured":"Wang Z, Kavdia K, Dey KK, Pagala VR, Kodali K, Liu D, et al. High-throughput and Deep-proteome Profiling by 16-plex Tandem Mass Tag Labeling Coupled with Two-dimensional Chromatography and Mass Spectrometry. Journal of Visualized Experiments. 2020;","DOI":"10.3791\/61684."},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Shaker H, Mourad MS, Elbialy MH, Elhilali M. Urinary bladder hyperreflexia: a rat animal model. Neurourology and Urodynamics. 2003; 22: 693\u2013698.","DOI":"10.1002\/nau.10147"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Scheff SW, Saucier DA, Cain ME. A Statistical Method for Analyzing Rating Scale Data: the BBB Locomotor Score. Journal of Neurotrauma. 2002; 19: 1251\u20131260.","DOI":"10.1089\/08977150260338038"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Xie C, Mao X, Huang J, Ding Y, Wu J, Dong S, et al. KOBAS 2.0: a web server for annotation and identification of enriched pathways and diseases. Nucleic Acids Research. 2011; 39: W316\u2013W322.","DOI":"10.1093\/nar\/gkr483"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, et al. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 2009; 25: 1091\u20131093.","DOI":"10.1093\/bioinformatics\/btp101"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Su G, Morris JH, Demchak B, Bader GD. Biological Network Exploration with Cytoscape 3. Current Protocols in Bioinformatics. 2014; 47: 8.13.1\u20138.13.24.","DOI":"10.1002\/0471250953.bi0813s47"},{"key":"ref16","unstructured":"Zhu Y, Huang J, Cheng J, Zhang WY, Yu J, Zhu LT. Effects of electro-acupuncture on myoelectric activity of detrusor and external urethra sphincter of complete T10 level spinal cord transection rats. Chinese Journal of Rehabilitation Medicine. 2013; 28: 124\u2013128."},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Sweeney HL, Hammers DW. Muscle Contraction. Cold Spring Harbor Perspectives in Biology. 2018; 10: a023200.","DOI":"10.1101\/cshperspect.a023200"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Xie Y, Han KH, Grainger N, Li W, Corrigan RD, Perrino BA. A role for focal adhesion kinase in facilitating the contractile responses of murine gastric fundus smooth muscles. The Journal of Physiology. 2018; 596: 2131\u20132146.","DOI":"10.1113\/JP275406"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Luo D, Wazir R, Tian Y, Yue X, Wei T, Wang K. Integrin \u03b1v Mediates Contractility whereas Integrin \u03b14 Regulates Proliferation of Human Bladder Smooth Muscle Cells via FAK Pathway under Physiological Stretch. Journal of Urology. 2013; 190: 1421\u20131429.","DOI":"10.1016\/j.juro.2013.04.027"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Xie P, Kondeti VK, Lin S, Haruna Y, Raparia K, Kanwar YS. Withdrawal: Role of extracellular matrix renal tubulo-interstitial nephritis antigen (TINag) in cell survival utilizing integrin \u03b1v\u03b23\/focal adhesion kinase (FAK)\/phosphatidylinositol 3-kinase (PI3K)\/protein kinase B-serine\/threonine kinase (AKT) signaling pathway. Journal of Biological Chemistry. 2019; 294: 10379.","DOI":"10.1074\/jbc.W119.009585"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"[21] Murthy KS, Zhou H, Grider JR, Brautigan DL, Eto M, Makhlouf GM. Differential signalling by muscarinic receptors in smooth muscle: m2-mediated inactivation of myosin light chain kinase via Gi3, Cdc42\/Rac1 and p21-activated kinase 1 pathway, and m3-mediated MLC20 (20 kDa regulatory light chain of myosin II) phosphorylation via Rho-associated kinase\/myosin phosphatase targeting subunit 1 and protein kinase C\/CPI-17 pathway. Biochemical Journal. 2003; 374: 145\u2013155.","DOI":"10.1042\/bj20021274"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Wang Y, Gratzke C, Tamalunas A, Wiemer N, Ciotkowska A, Rutz B, et al. P21-Activated Kinase Inhibitors FRAX486 and IPA3: Inhibition of Prostate Stromal Cell Growth and Effects on Smooth Muscle Contraction in the Human Prostate. PLoS ONE. 2016; 11: e0153312.","DOI":"10.1371\/journal.pone.0153312"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Horiguchi K, Hanada T, Fukui Y, Chishti AH. Transport of PIP3 by GAKIN, a kinesin-3 family protein, regulates neuronal cell polarity. Journal of Cell Biology. 2006; 174: 425\u2013436.","DOI":"10.1083\/jcb.200604031"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Stout KA, Dunn AR, Hoffman C, Miller GW. The Synaptic Vesicle Glycoprotein 2: Structure, Function, and Disease Relevance. ACS Chemical Neuroscience. 2019; 10: 3927\u20133938.","DOI":"10.1021\/acschemneuro.9b00351"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Ohno Y, Tokudome K. Therapeutic Role of Synaptic Vesicle Glycoprotein 2a (SV2a) in Modulating Epileptogenesis. CNS and Neurological Disorders - Drug Targets. 2017; 16: 463\u2013471.","DOI":"10.2174\/1871527316666170404115027"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Nowack A, Malarkey EB, Yao J, Bleckert A, Hill J, Bajjalieh SM. Levetiracetam reverses synaptic deficits produced by overexpression of SV2A. PLoS ONE. 2011; 6: e29560.","DOI":"10.1371\/journal.pone.0029560"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Vogl C, Tanifuji S, Danis B, Daniels V, Foerch P, Wolff C, et al. Synaptic vesicle glycoprotein 2a modulates vesicular release and calcium channel function at peripheral sympathetic synapses. European Journal of Neuroscience. 2015; 41: 398\u2013409.","DOI":"10.1111\/ejn.12799"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Touyz RM, Alves-Lopes R, Rios FJ, Camargo LL, Anagnostopoulou A, Arner A, et al. Vascular smooth muscle contraction in hypertension. Cardiovascular Research. 2018; 114: 529\u2013539.","DOI":"10.1093\/cvr\/cvy023"},{"key":"ref29","doi-asserted-by":"crossref","unstructured":"Mizuno Y, Isotani E, Huang J, Ding H, Stull JT, Kamm KE. Myosin light chain kinase activation and calcium sensitization in smooth muscle in vivo. American Journal of Physiology-Cell Physiology. 2008; 295: C358\u2013C364.","DOI":"10.1152\/ajpcell.90645.2007"},{"key":"ref30","doi-asserted-by":"crossref","unstructured":"Wleklinski MJ, Kannankeril PJ, Knollmann BC. Molecular and tissue mechanisms of catecholaminergic polymorphic ventricular tachycardia. The Journal of Physiology. 2020; 598: 2817\u20132834.","DOI":"10.1113\/JP276757"},{"key":"ref31","doi-asserted-by":"crossref","unstructured":"Lin JJ, Li Y, Eppinga RD, Wang Q, Jin JP. Chapter 1 Roles of Caldesmon in Cell Motility and Actin Cytoskeleton Remodeling. International Review of Cell and Molecular Biology. 2009; 274: 1\u201368.","DOI":"10.1016\/S1937-6448(08)02001-7"},{"key":"ref32","doi-asserted-by":"crossref","unstructured":"Liang C, Zhang G, Zhang L, Chen S, Wang J, Zhang T, et al. Calmodulin Bidirectionally Regulates Evoked and Spontaneous Neurotransmitter Release at Retinal Ribbon Synapses. Eneuro. 2021; 8: ENEURO.0257\u2013ENEU20.2020.","DOI":"10.1523\/ENEURO.0257-20.2020"},{"key":"ref33","doi-asserted-by":"crossref","unstructured":"P\u00fctz S, Barthel LS, Frohn M, Metzler D, Barham M, Pryymachuk G, et al. Caldesmon ablation in mice causes umbilical herniation and alters contractility of fetal urinary bladder smooth muscle. Journal of General Physiology. 2021; 153: e202012776.","DOI":"10.1085\/jgp.202012776"},{"key":"ref34","doi-asserted-by":"crossref","unstructured":"Vaes RDW, van den Berk L, Boonen B, van Dijk DPJ, Olde Damink SWM, Rensen SS. A novel human cell culture model to study visceral smooth muscle phenotypic modulation in health and disease. American Journal of Physiology-Cell Physiology. 2018; 315: C598\u2013C607.","DOI":"10.1152\/ajpcell.00167.2017"},{"key":"ref35","doi-asserted-by":"crossref","unstructured":"Valkovic AL, Bathgate RA, Samuel CS, Kocan M. Understanding relaxin signalling at the cellular level. Molecular and Cellular Endocrinology. 2019; 487: 24\u201333.","DOI":"10.1016\/j.mce.2018.12.017"},{"key":"ref36","doi-asserted-by":"crossref","unstructured":"Martin B, Romero G, Salama G. Cardioprotective actions of relaxin. Molecular and Cellular Endocrinology. 2019; 487: 45\u201353.","DOI":"10.1016\/j.mce.2018.12.016"},{"key":"ref37","doi-asserted-by":"crossref","unstructured":"Diaz EC, Briggs M, Wen Y, Zhuang G, Wallace SL, Dobberfuhl AD, et al. Characterizing relaxin receptor expression and exploring relaxin\u2019s effect on tissue remodeling\/fibrosis in the human bladder. BMC Urology. 2020; 20: 44.","DOI":"10.1186\/s12894-020-00607-4"},{"key":"ref38","doi-asserted-by":"crossref","unstructured":"Andersson K, Fry C, Panicker J, Rademakers K. Which molecular targets do we need to focus on to improve lower urinary tract dysfunction? ICI-RS 2017. Neurourology and Urodynamics. 2018; 37: S117\u2013S126.","DOI":"10.1002\/nau.23516"},{"key":"ref39","doi-asserted-by":"crossref","unstructured":"Lian X, Beer-Hammer S, K\u00f6nig GM, Kostenis E, N\u00fcrnberg B, Gollasch M. RXFP1 Receptor Activation by Relaxin-2 Induces Vascular Relaxation in Mice via a G\u03b1 i2-Protein\/PI3K\u00df\/\u03b3\/Nitric Oxide-Coupled Pathway. Frontiers in Physiology. 2018; 9: 1234.","DOI":"10.3389\/fphys.2018.01234"},{"key":"ref40","doi-asserted-by":"crossref","unstructured":"Matthees ESF, Haider RS, Hoffmann C. \u0392-arrestin\u2013based biosensors: Tools to explore structural determinants of metabolic functions? Current Opinion in Endocrine and Metabolic Research. 2021; 16: 66\u201374.","DOI":"10.1016\/j.coemr.2020.09.006"},{"key":"ref41","doi-asserted-by":"crossref","unstructured":"Gao H, Sun Y, Wu Y, Luan B, Wang Y, Qu B, et al. Identification of beta-arrestin2 as a G protein-coupled receptor-stimulated regulator of NF-kappaB pathways. Molecular Cell. 2004; 14: 303\u2013317.","DOI":"10.1016\/S1097-2765(04)00216-3"},{"key":"ref42","doi-asserted-by":"crossref","unstructured":"Stanasila L, Abuin L, Dey J, Cotecchia S. Different internalization properties of the alpha1a- and alpha1b-adrenergic receptor subtypes: the potential role of receptor interaction with beta-arrestins and AP50. Molecular Pharmacology. 2008; 74: 562\u2013573.","DOI":"10.1124\/mol.107.043422"},{"key":"ref43","doi-asserted-by":"crossref","unstructured":"Akinaga J, Garc\u00eda-S\u00e1inz JA, S Pupo A. Updates in the function and regulation of \u03b1 1 -adrenoceptors. British Journal of Pharmacology. 2019; 176: 2343\u20132357.","DOI":"10.1111\/bph.14617"}],"container-title":["Journal of Integrative Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.imrpress.com\/journal\/JIN\/21\/5\/10.31083\/j.jin2105147","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T15:54:48Z","timestamp":1732722888000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.imrpress.com\/journal\/JIN\/21\/5\/10.31083\/j.jin2105147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,26]]},"references-count":43,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022]]}},"alternative-id":["S0219-6352(22)00447-8"],"URL":"https:\/\/doi.org\/10.31083\/j.jin2105147","relation":{},"ISSN":["0219-6352","1757-448X"],"issn-type":[{"value":"0219-6352","type":"print"},{"value":"1757-448X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,26]]},"article-number":"147"}}