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The effect of rapamycin on TGFβ1 and MMP1 expression in a rabbit model of urethral stricture

  • Urology - Original Paper
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Abstract

Purpose

To investigate the effect of rapamycin on TGFβ1 and MMP1 expression in a rabbit model of urethral stricture.

Methods

Twenty-four adult New Zealand male rabbits underwent an electrocoagulation of the bulbar urethra with a 13Fr pediatric resectoscope. Then rabbits were randomly divided into three groups: (1) normal control group: normal saline (NS), (2) the vehicle control group: dimethyl sulfoxide (DMSO), and (3) the treatment group: effective-dose rapamycin in DMSO (Ra), with 12, 6, and 6 rabbits in each group, respectively. Drugs were given by urethral irrigation daily for 4 weeks. Urethral tissue was harvested for histological and molecular analyses. TGFβ1 and MMP1 expression levels were evaluated by real-time quantitative PCR and immunohistochemistry.

Results

Ten, six, and six rabbits were evaluated finally in Ra, DMSO, and NS group, respectively. Histological examination revealed the distribution of fibrosis and the degree of collagen deposition in the Ra group were smaller and slighter than the two control groups. Collagen content was significantly less in the Ra group than in the DMSO group (P < 0.001) and the NS group (P < 0.001). qRT-PCR analysis showed a higher expression of MMP1 mRNA in the Ra group than in the DMSO group (P < 0.001) and the NS group (P < 0.001). Immunohistochemistry showed the protein levels of MMP1 in the Ra group were significantly increased when compared with the DMSO group (P < 0.01) and the NS group (P < 0.01). On the other hand, no statistical difference could be found between every two groups in both mRNA and protein levels of TGFβ1.

Conclusions

Rapamycin enhances the expression of MMP1 in a rabbit model of urethral stricture, but has no direct effect on the expression of TGFβ1.

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Acknowledgments

We appreciate Zhao XG (Xi’an Jiaotong University) for his help with pathological analysis and Li M (Xi’an Jiaotong University) for her help with statistical analysis. And we also appreciate the National Natural Science Foundation of China (No. 30972977) that provided the funds for this study.

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Authors and Affiliations

  1. Department of Urology, the Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, Xi’an City, 710004, Shaanxi Province, People’s Republic of China

    S. L. Huang, D. L. Fu, H. C. Li, P. Zhang & T. Chong

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  1. S. L. Huang
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  2. D. L. Fu
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  3. H. C. Li
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  4. P. Zhang
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Correspondence to T. Chong.

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The authors have declared that no competing interests exist.

Human and animal rights

All experiments were performed according to the guidelines of the committee of animal research at Xi’an Jiaotong University and the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health.

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Huang, S.L., Fu, D.L., Li, H.C. et al. The effect of rapamycin on TGFβ1 and MMP1 expression in a rabbit model of urethral stricture. Int Urol Nephrol 48, 717–723 (2016). https://doi.org/10.1007/s11255-016-1227-x

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  • DOI: https://doi.org/10.1007/s11255-016-1227-x

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