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Sodium Tanshinone IIA Sulfonate Ameliorates Bladder Fibrosis in a Rat Model of Partial Bladder Outlet Obstruction by Inhibiting the TGF-β/Smad Pathway Activation.

Jiang X, Chen Y, Zhu H, Wang B, Qu P, Chen R, Sun X - PLoS ONE (2015)

Bottom Line: 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.The TGF-β/Smad signaling pathway was analyzed using western blotting, immunohistochemical staining and reverse transcriptase polymerase chain reaction (RT-PCR).

View Article: PubMed Central - PubMed

Affiliation: Xuzhou Medical College, Xuzhou, Jiangsu, China; Department of Urologic Surgery, Yancheng City No.1 People's Hospital, Yancheng, Jiangsu, China.

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.

No MeSH data available.


Related in: MedlinePlus

H&E-stained paraffin-embedded rat bladder sections.In PBOO rats, significant detrusor muscle hypertrophy, alongside a progressive increase in fibrosis (dyed pale pink, blue arrow) and loss of normal muscle tissue (dyed purple or red, black arrow)architecture was observable at 4 and 8 weeks of PBOO. Fibrosis was inhibited in the STS group at (a) week 4 in Sham group, (b) week 4 after PBOO, (c) week 4 after PBOO+STS treatment, (d) week 8 after Sham group, (e) week 8 after PBOO, and(f) week 8 after PBOO+STS treatment. The PBOO and STS groups show detrusor hypertrophy and collagen deposition. Original magnifications, ×40.
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pone.0129655.g001: H&E-stained paraffin-embedded rat bladder sections.In PBOO rats, significant detrusor muscle hypertrophy, alongside a progressive increase in fibrosis (dyed pale pink, blue arrow) and loss of normal muscle tissue (dyed purple or red, black arrow)architecture was observable at 4 and 8 weeks of PBOO. Fibrosis was inhibited in the STS group at (a) week 4 in Sham group, (b) week 4 after PBOO, (c) week 4 after PBOO+STS treatment, (d) week 8 after Sham group, (e) week 8 after PBOO, and(f) week 8 after PBOO+STS treatment. The PBOO and STS groups show detrusor hypertrophy and collagen deposition. Original magnifications, ×40.

Mentions: Paraffin-embedded sections from PBOO operation without STS treatment group and PBOO operation with STS treatment groups were stained with hematoxylin and eosin and examined. The two groups of rats which had undergone PBOO procedure exhibited significant bladder detrusor hypertrophy at weeks 4 and 8. Furthermore, a progressive increase in fibrosis and loss of normal tissue architecture from week 4 to 8 was observed in the group which had not been administered STS. However, fibrosis was inhibited in the group which had been treated with STS (Fig 1).


Sodium Tanshinone IIA Sulfonate Ameliorates Bladder Fibrosis in a Rat Model of Partial Bladder Outlet Obstruction by Inhibiting the TGF-β/Smad Pathway Activation.

Jiang X, Chen Y, Zhu H, Wang B, Qu P, Chen R, Sun X - PLoS ONE (2015)

H&E-stained paraffin-embedded rat bladder sections.In PBOO rats, significant detrusor muscle hypertrophy, alongside a progressive increase in fibrosis (dyed pale pink, blue arrow) and loss of normal muscle tissue (dyed purple or red, black arrow)architecture was observable at 4 and 8 weeks of PBOO. Fibrosis was inhibited in the STS group at (a) week 4 in Sham group, (b) week 4 after PBOO, (c) week 4 after PBOO+STS treatment, (d) week 8 after Sham group, (e) week 8 after PBOO, and(f) week 8 after PBOO+STS treatment. The PBOO and STS groups show detrusor hypertrophy and collagen deposition. Original magnifications, ×40.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4464658&req=5

pone.0129655.g001: H&E-stained paraffin-embedded rat bladder sections.In PBOO rats, significant detrusor muscle hypertrophy, alongside a progressive increase in fibrosis (dyed pale pink, blue arrow) and loss of normal muscle tissue (dyed purple or red, black arrow)architecture was observable at 4 and 8 weeks of PBOO. Fibrosis was inhibited in the STS group at (a) week 4 in Sham group, (b) week 4 after PBOO, (c) week 4 after PBOO+STS treatment, (d) week 8 after Sham group, (e) week 8 after PBOO, and(f) week 8 after PBOO+STS treatment. The PBOO and STS groups show detrusor hypertrophy and collagen deposition. Original magnifications, ×40.
Mentions: Paraffin-embedded sections from PBOO operation without STS treatment group and PBOO operation with STS treatment groups were stained with hematoxylin and eosin and examined. The two groups of rats which had undergone PBOO procedure exhibited significant bladder detrusor hypertrophy at weeks 4 and 8. Furthermore, a progressive increase in fibrosis and loss of normal tissue architecture from week 4 to 8 was observed in the group which had not been administered STS. However, fibrosis was inhibited in the group which had been treated with STS (Fig 1).

Bottom Line: 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.The TGF-β/Smad signaling pathway was analyzed using western blotting, immunohistochemical staining and reverse transcriptase polymerase chain reaction (RT-PCR).

View Article: PubMed Central - PubMed

Affiliation: Xuzhou Medical College, Xuzhou, Jiangsu, China; Department of Urologic Surgery, Yancheng City No.1 People's Hospital, Yancheng, Jiangsu, China.

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.

No MeSH data available.


Related in: MedlinePlus