title: Crosstalk between TGF-β1 and CXCR3 signaling during urethral fibrosis.
abstract: Urethral fibrosis is an important pathological feature of urethral stricture. TGF-β1 and CXC chemokine receptor 3 (CXCR3) signaling have been reported as the critical pathways involved in the pathology of fibrosis. Here, we collected the urine samples from the patients with recurring urethral stricture, recurring stricture treated by cystostomy, and age- and gender-matched healthy people. ELISA detection revealed that TGF-β1 level was significantly up-regulated for the urethral stricture patients. By contrast, flow cytometry, real-time PCR detection, and immunofluoresecent staining showed that urethral stricture resulted in decreased expression of CXCR3. TGF-β1 treatment could increase cell proliferation and migration ability of urethra fibroblasts, whereas IP-10/CXCR3 signaling showed the opposite effect. Further, we found a crosstalk between TGF-β1 and CXCR3 signaling in the regulation of urethral fibrosis. Thus, pharmacological intervention of TGF-β1 or CXCR3 signaling has a potential as the therapeutic target for the prevention of urethral fibrosis.
authors.affiliation: Department of Urology, Shanghai Jiaotong University Affiliated Shanghai Sixth Hospital, Shanghai, 200233, People's Republic of China, goldguo1973@sina.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Xie
authors.forename: Chao
authors.initials: C
authors.lastname: Feng
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.forename: Ying-Long
authors.initials: YL
authors.lastname: Sa
authors.forename: Yue-Min
authors.initials: YM
authors.lastname: Xu
mesh_terms: D016022:Case-Control Studies; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D003559:Cystostomy; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D000077294:Receptor, Transforming Growth Factor-beta Type II; D054367:Receptors, CXCR3 / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D012008:Recurrence; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000652:urine; D014521:Urethra / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D014525:Urethral Stricture / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery / Q000652:urine
chemical_list: C515187:CXCR3 protein, human; D054367:Receptors, CXCR3; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II