{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T19:25:23Z","timestamp":1785525923279,"version":"3.56.0"},"reference-count":71,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T00:00:00Z","timestamp":1679011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004329","name":"Slovenian Research Agency","doi-asserted-by":"publisher","award":["J3-2521"],"award-info":[{"award-number":["J3-2521"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004329","name":"Slovenian Research Agency","doi-asserted-by":"publisher","award":["P3-0108"],"award-info":[{"award-number":["P3-0108"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004329","name":"Slovenian Research Agency","doi-asserted-by":"publisher","award":["P3-0314"],"award-info":[{"award-number":["P3-0314"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Animal models are invaluable in the research of the pathophysiology of interstitial cystitis\/bladder pain syndrome (IC\/BPS), a chronic aseptic urinary bladder disease of unknown etiology that primarily affects women. Here, a mouse model of IC\/BPS was induced with multiple low-dose cyclophosphamide (CYP) applications and thoroughly characterized by RNA sequencing, qPCR, Western blot, and immunolabeling to elucidate key inflammatory processes and sex-dependent differences in the bladder inflammatory response. CYP treatment resulted in the upregulation of inflammatory transcripts such as Ccl8, Eda2r, and Vegfd, which are predominantly involved in innate immunity pathways, recapitulating the crucial findings in the bladder transcriptome of IC\/BPS patients. The JAK\/STAT signaling pathway was analyzed in detail, and the JAK3\/STAT3 interaction was found to be most activated in cells of the bladder urothelium and lamina propria. Sex-based data analysis revealed that cell proliferation was more pronounced in male bladders, while innate immunity and tissue remodeling processes were the most distinctive responses of female bladders to CYP treatment. These processes were also reflected in prominent histological changes in the bladder. The study provides an invaluable reference dataset for preclinical research on IC\/BPS and an insight into the sex-specific mechanisms involved in the development of IC\/BPS pathology, which may explain the more frequent occurrence of this disease in women.<\/jats:p>","DOI":"10.3390\/ijms24065758","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T04:33:31Z","timestamp":1679286811000},"page":"5758","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Molecular Profiling of Inflammatory Processes in a Mouse Model of IC\/BPS: From the Complete Transcriptome to Major Sex-Related Histological Features of the Urinary Bladder"],"prefix":"10.3390","volume":"24","author":[{"given":"Dominika","family":"Peskar","sequence":"first","affiliation":[{"name":"Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4749-594X","authenticated-orcid":false,"given":"Tadeja","family":"Kuret","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8062-7908","authenticated-orcid":false,"given":"Katja","family":"Lakota","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Medical Center Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreja","family":"Erman","sequence":"additional","affiliation":[{"name":"Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1097\/JU.0000000000002756","article-title":"Diagnosis and Treatment of Interstitial Cystitis\/Bladder Pain Syndrome","volume":"208","author":"Clemens","year":"2022","journal-title":"J. Urol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/iju.13969","article-title":"Phenotyping of interstitial cystitis\/bladder pain syndrome","volume":"26","author":"Akiyama","year":"2019","journal-title":"Int. J. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Li, J., Yi, X., and Ai, J. (2022). Broaden Horizons: The Advancement of Interstitial Cystitis\/Bladder Pain Syndrome. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314594"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1002\/nau.21078","article-title":"Models of inflammation of the lower urinary tract","volume":"30","author":"Bjorling","year":"2011","journal-title":"Neurourol. Urodyn."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kuret, T., Peskar, D., Erman, A., and Verani\u010d, P. (2021). A Systematic Review of Therapeutic Approaches Used in Experimental Models of Interstitial Cystitis\/Bladder Pain Syndrome. Biomedicines, 9.","DOI":"10.3390\/biomedicines9080865"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1002\/nau.21180","article-title":"Functional characterization of a chronic cyclophosphamide-induced overactive bladder model in mice","volume":"30","author":"Boudes","year":"2011","journal-title":"Neurourol. Urodyn."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e00260","DOI":"10.1002\/phy2.260","article-title":"The mouse cyclophosphamide model of bladder pain syndrome: Tissue characterization, immune profiling, and relationship to metabotropic glutamate receptors","volume":"2","author":"Golubeva","year":"2014","journal-title":"Physiol. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1111\/j.1464-410X.2007.06773.x","article-title":"Acute acrolein-induced cystitis in mice","volume":"99","author":"Bjorling","year":"2007","journal-title":"BJU Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1016\/0006-2952(79)90222-3","article-title":"Cyclophosphamide cystitis--identification of acrolein as the causative agent","volume":"28","author":"Cox","year":"1979","journal-title":"Biochem. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"F1391","DOI":"10.1152\/ajprenal.00051.2020","article-title":"Urine cytokines as biomarkers for diagnosing interstitial cystitis\/bladder pain syndrome and mapping its clinical characteristics","volume":"318","author":"Jiang","year":"2020","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Jiang, Y.H., Peng, C.H., Liu, H.T., and Kuo, H.C. (2013). Increased pro-inflammatory cytokines, C-reactive protein and nerve growth factor expressions in serum of patients with interstitial cystitis\/bladder pain syndrome. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076779"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1097\/JU.0000000000000234","article-title":"Molecular Taxonomy of Interstitial Cystitis\/Bladder Pain Syndrome Based on Whole Transcriptome Profiling by Next-Generation RNA Sequencing of Bladder Mucosal Biopsies","volume":"202","author":"Akiyama","year":"2019","journal-title":"J. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Gheinani, A.H., Akshay, A., Besic, M., Kuhn, A., Keller, I., Bruggmann, R., Rehrauer, H., Adam, R.M., Burkhard, F.C., and Monastyrskaya, K. (2021). Integrated mRNA-miRNA transcriptome analysis of bladder biopsies from patients with bladder pain syndrome identifies signaling alterations contributing to the disease pathogenesis. BMC Urol., 21.","DOI":"10.1186\/s12894-021-00934-0"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s12967-022-03236-7","article-title":"Immune cell profiles of patients with interstitial cystitis\/bladder pain syndrome","volume":"20","author":"Moldwin","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"925834","DOI":"10.3389\/fpain.2022.925834","article-title":"National prevalence of IC\/BPS in women and men utilizing veterans health administration data","volume":"3","author":"Anger","year":"2022","journal-title":"Front. Pain Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1097\/01.ju.0000165170.43617.be","article-title":"Prevalence of interstitial cystitis symptoms in a managed care population","volume":"174","author":"Clemens","year":"2005","journal-title":"J. Urol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"954967","DOI":"10.3389\/fpain.2022.954967","article-title":"Gender differences in the experience of interstitial cystitis\/bladder pain syndrome","volume":"3","author":"Windgassen","year":"2022","journal-title":"Front. Pain. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1128\/microbiolspec.UTI-0024-2016","article-title":"Innate Immune Responses to Bladder Infection","volume":"4","author":"Hayes","year":"2016","journal-title":"Microbiol. Spectr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e2106063","DOI":"10.1002\/advs.202106063","article-title":"Multimodal Single-Cell Analyses Outline the Immune Microenvironment and Therapeutic Effectors of Interstitial Cystitis\/Bladder Pain Syndrome","volume":"9","author":"Su","year":"2022","journal-title":"Adv. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"106210","DOI":"10.1016\/j.intimp.2020.106210","article-title":"The role of JAK\/STAT signaling pathway and its inhibitors in diseases","volume":"80","author":"Xin","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41392-021-00791-1","article-title":"The JAK\/STAT signaling pathway: From bench to clinic","volume":"6","author":"Hu","year":"2021","journal-title":"Signal. Transduct. Target Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s12964-017-0177-y","article-title":"The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells","volume":"15","author":"Seif","year":"2017","journal-title":"Cell Commun. Signal"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.urology.2006.08.1111","article-title":"Contemporary clinical presentation of interstitial cystitis","volume":"69","author":"Teichman","year":"2007","journal-title":"Urology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"11682","DOI":"10.1074\/jbc.272.18.11682","article-title":"Monocyte chemotactic protein-2 (MCP-2) uses CCR1 and CCR2B as its functional receptors","volume":"272","author":"Gong","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1086\/339678","article-title":"Monocyte chemoattractant protein-2 (CC chemokine ligand 8) inhibits replication of human immunodeficiency virus type 1 via CC chemokine receptor 5","volume":"185","author":"Yang","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"eabd4550","DOI":"10.1126\/scitranslmed.abd4550","article-title":"Macrophage depletion induces edema through release of matrix-degrading proteases and proteoglycan deposition","volume":"13","author":"Bissinger","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.pmbts.2017.02.005","article-title":"Biochemical and Biological Attributes of Matrix Metalloproteinases","volume":"147","author":"Cui","year":"2017","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.5213\/inj.1835062.531","article-title":"Animal Modelling of Interstitial Cystitis\/Bladder Pain Syndrome","volume":"22","author":"Birder","year":"2018","journal-title":"Int. Neurourol. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3389\/fnins.2011.00020","article-title":"Increased expression of interleukin-6 family members and receptors in urinary bladder with cyclophosphamide-induced bladder inflammation in female rats","volume":"5","author":"Girard","year":"2011","journal-title":"Front. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"R677","DOI":"10.1152\/ajpregu.00305.2007","article-title":"Expression of cyclooxygenase-2 in urinary bladder in rats with cyclophosphamide-induced cystitis","volume":"293","author":"Klinger","year":"2007","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"960667","DOI":"10.3389\/fimmu.2022.960667","article-title":"Comprehensive transcriptome profiling of urothelial cells following TNF\u03b1 stimulation in an in vitro interstitial cystitis\/bladder pain syndrome model","volume":"13","author":"Kuret","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"755615","DOI":"10.3389\/fphar.2021.755615","article-title":"A Novel Intravesical Dextrose Injection Improves Lower Urinary Tract Symptoms on Interstitial Cystitis\/Bladder Pain Syndrome","volume":"12","author":"Chen","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"F741","DOI":"10.1152\/ajprenal.00081.2006","article-title":"Urothelial lesion formation is mediated by TNFR1 during neurogenic cystitis","volume":"291","author":"Chen","year":"2006","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.4238\/2013.May.6.1","article-title":"Gene expression profile and enrichment pathways in different stages of bladder cancer","volume":"12","author":"Fang","year":"2013","journal-title":"Genet Mol. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12957-018-1555-7","article-title":"The role of oncostatin M receptor gene polymorphisms in bladder cancer","volume":"17","author":"Deng","year":"2019","journal-title":"World J. Surg. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/ibd.20344","article-title":"Suppression of colon inflammation by CD80 blockade: Evaluation in two murine models of inflammatory bowel disease","volume":"14","author":"Eri","year":"2008","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/s42003-021-01730-0","article-title":"Macrophage-derived EDA-A2 inhibits intestinal stem cells by targeting miR-494\/EDA2R\/\u03b2-catenin signaling in mice","volume":"4","author":"Song","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"F1038","DOI":"10.1152\/ajprenal.00110.2009","article-title":"Involvement of JAK-STAT signaling\/function after cyclophosphamide-induced bladder inflammation in female rats","volume":"297","author":"Cheppudira","year":"2009","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9147","DOI":"10.1002\/jcb.28190","article-title":"Inhibition of microRNA-132 attenuates inflammatory response and detrusor fibrosis in rats with interstitial cystitis via the JAK-STAT signaling pathway","volume":"120","author":"Song","year":"2019","journal-title":"J. Cell Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1007\/s00192-020-04593-x","article-title":"MicroRNA-495 alleviates ulcerative interstitial cystitis via inactivating the JAK-STAT signaling pathway by inhibiting JAK3","volume":"32","author":"Hou","year":"2021","journal-title":"Int. Urogynecol. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1016\/j.kint.2017.12.006","article-title":"Interleukin-6\/Stat3 signaling has an essential role in the host antimicrobial response to urinary tract infection","volume":"93","author":"Ching","year":"2018","journal-title":"Kidney Int."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.imbio.2005.05.001","article-title":"Tuning of macrophage responses by Stat3-inducing cytokines: Molecular mechanisms and consequences in infection","volume":"210","author":"Lang","year":"2005","journal-title":"Immunobiology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.cyto.2009.07.003","article-title":"STAT3 in CD4+ T helper cell differentiation and inflammatory diseases","volume":"47","author":"Egwuagu","year":"2009","journal-title":"Cytokine"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1084\/jem.20130323","article-title":"Naive and memory human B cells have distinct requirements for STAT3 activation to differentiate into antibody-secreting plasma cells","volume":"210","author":"Deenick","year":"2013","journal-title":"J. Exp. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1038\/s41467-017-01236-6","article-title":"Activation of STAT3 integrates common profibrotic pathways to promote fibroblast activation and tissue fibrosis","volume":"8","author":"Chakraborty","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1593\/neo.13952","article-title":"STAT3 in Epithelial Cells Regulates Inflammation and Tumor Progression to Malignant State in Colon","volume":"15","author":"Nguyen","year":"2013","journal-title":"Neoplasia"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6424","DOI":"10.7150\/thno.35528","article-title":"Targeted inhibition of STAT3 as a potential treatment strategy for atherosclerosis","volume":"9","author":"Chen","year":"2019","journal-title":"Theranostics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"H2101","DOI":"10.1152\/ajpheart.00125.2007","article-title":"Endothelial STAT3 plays a critical role in generalized myocardial proinflammatory and proapoptotic signaling","volume":"293","author":"Wang","year":"2007","journal-title":"Am. J. Physiol. Heart Circ Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e149538","DOI":"10.1172\/JCI149538","article-title":"Fibroblast pathology in inflammatory diseases","volume":"131","author":"Wei","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.immuni.2016.02.015","article-title":"Macrophages in Tissue Repair, Regeneration, and Fibrosis","volume":"44","author":"Wynn","year":"2016","journal-title":"Immunity"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1007\/s12016-017-8648-x","article-title":"Sexual Dimorphism in Innate Immunity","volume":"56","author":"Jaillon","year":"2019","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4295","DOI":"10.1038\/s41467-019-12348-6","article-title":"ImmGen report: Sexual dimorphism in the immune system transcriptome","volume":"10","author":"Maier","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/s43587-021-00086-8","article-title":"Multi-omic profiling of primary mouse neutrophils predicts a pattern of sex and age-related functional regulation","volume":"1","author":"Lu","year":"2021","journal-title":"Nat. Aging"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/s41585-020-0350-8","article-title":"The immune response to infection in the bladder","volume":"17","author":"Ingersoll","year":"2020","journal-title":"Nat. Rev. Urol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1681\/ASN.2019040335","article-title":"Single-Cell Transcriptomic Map of the Human and Mouse Bladders","volume":"30","author":"Yu","year":"2019","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7802","DOI":"10.1038\/ncomms8802","article-title":"Intestinal CD169(+) macrophages initiate mucosal inflammation by secreting CCL8 that recruits inflammatory monocytes","volume":"6","author":"Asano","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.brainresbull.2017.10.009","article-title":"Chemokine CCL8 and its receptor CCR5 in the spinal cord are involved in visceral pain induced by experimental colitis in mice","volume":"135","author":"Lu","year":"2017","journal-title":"Brain. Res. Bull"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/0090-4295(78)90286-8","article-title":"Interstitial cystitis: Early diagnosis, pathology, and treatment","volume":"12","author":"Messing","year":"1978","journal-title":"Urology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/S0022-5347(17)40201-1","article-title":"Clinical features and spectrum of light microscopic changes in interstitial cystitis","volume":"143","author":"Johansson","year":"1990","journal-title":"J. Urol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.3389\/fphar.2020.01305","article-title":"Characterization and Validation of a Chronic Model of Cyclophosphamide-Induced Interstitial Cystitis\/Bladder Pain Syndrome in Rats","volume":"11","author":"Vergnolle","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1159\/000328248","article-title":"Contribution of matrix metalloproteinase-9 to cerebral edema and functional outcome following experimental subarachnoid hemorrhage","volume":"32","author":"Feiler","year":"2011","journal-title":"Cerebrovasc. Dis."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Trentini, A., Manfrinato, M.C., Castellazzi, M., and Bellini, T. (2022). Sex-Related Differences of Matrix Metalloproteinases (MMPs): New Perspectives for These Biomarkers in Cardiovascular and Neurological Diseases. J. Pers. Med., 12.","DOI":"10.3390\/jpm12081196"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1146\/annurev.cellbio.17.1.463","article-title":"How matrix metalloproteinases regulate cell behavior","volume":"17","author":"Sternlicht","year":"2001","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"F732","DOI":"10.1152\/ajprenal.00337.2016","article-title":"Sleeping beauty: Awakening urothelium from its slumber","volume":"312","author":"Balsara","year":"2017","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/s41419-021-03740-6","article-title":"Single-cell analysis reveals urothelial cell heterogeneity and regenerative cues following cyclophosphamide-induced bladder injury","volume":"12","author":"Cheng","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e13007","DOI":"10.1111\/cpr.13007","article-title":"Single-cell transcriptomes of mouse bladder urothelium uncover novel cell type markers and urothelial differentiation characteristics","volume":"54","author":"Li","year":"2021","journal-title":"Cell Prolif."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1111\/his.13235","article-title":"Histopathological characteristics of interstitial cystitis\/bladder pain syndrome without Hunner lesion","volume":"71","author":"Kim","year":"2017","journal-title":"Histopathology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1016\/S0090-4295(03)00005-0","article-title":"Decreased in vitro proliferation of bladder epithelial cells from patients with interstitial cystitis","volume":"61","author":"Keay","year":"2003","journal-title":"Urology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"W566","DOI":"10.1093\/nar\/gkv468","article-title":"ClustVis: A web tool for visualizing clustering of multivariate data using Principal Component Analysis and heatmap","volume":"43","author":"Metsalu","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein-protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5758\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:57:34Z","timestamp":1760122654000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/6\/5758"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,17]]},"references-count":71,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijms24065758"],"URL":"https:\/\/doi.org\/10.3390\/ijms24065758","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,17]]}}}