title: Connective tissue and its growth factor CTGF distinguish the morphometric and molecular remodeling of the bladder in a model of neurogenic bladder.
abstract: We previously reported that mice with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), develop profound urinary bladder dysfunction. Because neurogenic bladder in MS patients causes marked bladder remodeling, we next examined morphometric and molecular alterations of the bladder in EAE mice. EAE was created in female SJL/J mice by immunization with the p139-151 encephalitogenic peptide of myelin proteolipid protein in complete Freund's adjuvant, along with intraperitoneal injections of Bordetella pertussis toxin. Seventy days after immunization, mice were scored for the level of neurological impairment and then killed. Spinal cord sections were assessed for demyelination, inflammation, and T cell infiltration; the composition of the bladder tissue was measured quantitatively; and gene expression of markers of tissue remodeling and fibrosis was assessed. A significant increase in the bladder weight-to-body weight ratio was observed with increasing neurological impairment, and morphometric analysis showed marked bladder remodeling with increased luminal area and tissue hypertrophy. Despite increased amounts of all tissue components (urothelium, smooth muscle, and connective tissue), the ratio of connective tissue to muscle increased significantly in EAE mice compared with control mice. Marked increases in mRNA expression of collagen type I α(2), tropoelastin, transforming growth factor-β3, and connective tissue growth factor (CTGF) were observed in EAE mice, as were decreased levels of mRNAs for smooth muscle myosin heavy chain, nerve growth factors, and muscarinic and purinergic receptors. Our results suggest that bladder remodeling corresponding to EAE severity may be due to enhanced expression of CTGF and increased growth of connective tissue.
authors.affiliation: Urology Institute, Univ. Hospitals Case Medical Center; Dept. of Urology, Case Western Reserve Univ. School of Medicine; 11100 Euclid Ave., Lakeside Bldg., Ste. 4554, Cleveland, OH 44106, USA.
authors.forename: Cengiz Z
authors.initials: CZ
authors.lastname: Altuntas
authors.forename: Firouz
authors.initials: F
authors.lastname: Daneshgari
authors.forename: Kenan
authors.initials: K
authors.lastname: Izgi
authors.forename: Fuat
authors.initials: F
authors.lastname: Bicer
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ozer
authors.forename: Cagri
authors.initials: C
authors.lastname: Sakalar
authors.forename: Kerry O
authors.initials: KO
authors.lastname: Grimberg
authors.forename: Ismail
authors.initials: I
authors.lastname: Sayin
authors.forename: Vincent K
authors.initials: VK
authors.lastname: Tuohy
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000378:metabolism; D003238:Connective Tissue / Q000473:pathology* / Q000503:physiopathology*; D055513:Connective Tissue Growth Factor / Q000502:physiology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications; D005260:Female; D006984:Hypertrophy; D051379:Mice; D008815:Mice, Inbred Strains; D009103:Multiple Sclerosis / Q000150:complications; D012333:RNA, Messenger / Q000378:metabolism; D053782:Transforming Growth Factor beta3 / Q000378:metabolism; D014333:Tropoelastin / Q000378:metabolism; D001743:Urinary Bladder / Q000473:pathology* / Q000503:physiopathology*; D001750:Urinary Bladder, Neurogenic / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*
chemical_list: C526318:CCN2 protein, mouse; D024042:Collagen Type I; D012333:RNA, Messenger; D053782:Transforming Growth Factor beta3; D014333:Tropoelastin; D055513:Connective Tissue Growth Factor