title: The effect of rapamycin on TGFβ1 and MMP1 expression in a rabbit model of urethral stricture.
abstract: OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: S L
authors.initials: SL
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: D L
authors.initials: DL
authors.lastname: Fu
authors.affiliation: 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.
authors.forename: H C
authors.initials: HC
authors.lastname: Li
authors.affiliation: 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.
authors.forename: P
authors.initials: P
authors.lastname: Zhang
authors.affiliation: 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. 307871779@qq.com.
authors.forename: T
authors.initials: T
authors.lastname: Chong
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D003094:Collagen / Q000032:analysis; D004195:Disease Models, Animal; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000032:analysis* / Q000235:genetics; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D020123:Sirolimus / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000032:analysis* / Q000235:genetics; D014525:Urethral Stricture / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D000903:Antibiotics, Antineoplastic; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D003094:Collagen; D020781:Matrix Metalloproteinase 1; D020123:Sirolimus
keywords: MMP1; Rapamycin; TGFβ1; Urethral stricture
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