title: Sodium Tanshinone IIA Sulfonate Ameliorates Bladder Fibrosis in a Rat Model of Partial Bladder Outlet Obstruction by Inhibiting the TGF-β/Smad Pathway Activation.
abstract: Transforming growth factor (TGF)-β1 is known to play a pivotal role in a diverse range of biological systems including modulation of fibrosis in several organs. The precise role of TGF-β/Smad signaling in the progression of bladder fibrosis secondary to partial bladder outlet obstruction (PBOO) is yet to be conclusively. Using a rat PBOO model, we investigated TGF-β1 expression and exaimined whether sodium tanshinone IIA sulfonate (STS) could inhibit TGF-β/Smad signaling pathway activation and ameliorate bladder fibrosis. Forty-eight female Sprague-Dawley rats were randomly divided into three groups: sham operation group (n = 16), PBOO operation without STS treatment group (n = 16) and PBOO operation with STS treatment group (n = 16). Thirty-two rats underwent the operative procedure to create PBOO and subsequently received intraperitoneal injections of STS (10 mg/kg/d; n = 16) or vehicle (n = 16) two days after the surgery. Sham surgery was conducted on 16 rats, which received intraperitoneal vehicle injection two days later. In each of the three groups, an equal number of rats were sacrificed at weeks 4 and 8 after the PBOO or sham operation. The TGF-β/Smad signaling pathway was analyzed using western blotting, immunohistochemical staining and reverse transcriptase polymerase chain reaction (RT-PCR). One-way analysis of variance was conducted to draw statistical inferences. At 4 and 8 weeks, the expression of TGF-β1 and phosphorylated Smad2 and Smad3 in STS-treated PBOO rats was significantly lower than in the PBOO rats not treated with STS. Alpha smooth muscle actin (α-SMA), collagen I and collagen III expression at 4 and 8 weeks post PBOO was lower in STS-treated PBOO rats when compared to that in PBOO rats not treated with STS. Our findings indicate that STS ameliorates bladder fibrosis by inhibiting TGF-β/Smad signaling pathway activation, and may prove to be a potential therapeutic measure for preventing bladder fibrosis secondary to PBOO operation.
authors.affiliation: Xuzhou Medical College, Xuzhou, Jiangsu, China; Department of Urologic Surgery, Yancheng City No.1 People's Hospital, Yancheng, Jiangsu, China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Xuzhou Medical College, Xuzhou, Jiangsu, China; Department of Oncology, Yancheng City No.1 People's Hospital, Yancheng, Jiangsu, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Xuzhou Medical College, Xuzhou, Jiangsu, China; Department of Urologic Surgery, the Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Urologic Surgery, Yancheng City No.1 People's Hospital, Yancheng, Jiangsu, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Qu
authors.affiliation: Department of Urologic Surgery, the Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Renfu
authors.initials: R
authors.lastname: Chen
authors.affiliation: Xuzhou Medical College, Xuzhou, Jiangsu, China; Department of Urologic Surgery, the Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China; Department of Urologic Laboratory, Xuzhou Medical Affiliated Hospital, Xuzhou, Jiangsu, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D005260:Female; D005355:Fibrosis; D010616:Phenanthrenes / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001748:Urinary Bladder Neck Obstruction / Q000188:drug therapy*
chemical_list: D010616:Phenanthrenes; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; C024894:tanshinone II A sodium sulfonate