Preliminary experimental study of urethral reconstruction with tissue engineering and RNA interference techniques

Li, Chao; Xu, Yue-Min; Li, Hongbin

doi:10.1038/aja.2013.2

Cited by 9 publications

(9 citation statements)

References 23 publications

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“…Although TIMP-1 has been recently recognized to play a role in the urethral scar formation, it is mainly thought to inhibit collagenase activity [5][6][7][8]23]. The effect of TIMP-1 on fibroblast transformation, however, has not been studied.…”

Section: Discussionmentioning

confidence: 96%

“…Thus efficient therapeutic interventions, e.g. inhibition of fibrosis, or decrease of collagen deposition, or increase of collagenolysis, are highly needed [5][6][7][8].…”

Section: Discussionmentioning

confidence: 99%

“…The molecular basis of urethral stricture involves activation of tissue fibroblasts, their transformation into myofibroblasts, following outgrowth and increased deposition of collagens, and consequent changes in extracellular matrix components [5][6][7][8]. The matrix metalloproteinase (MMP) family members are involved in the breakdown of extracellular matrix during embryonic development, tissue remodeling and disease processes [9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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TIMP-1 Induces α-Smooth Muscle Actin in Fibroblasts to Promote Urethral Scar Formation

et al. 2015

Cell Physiol Biochem

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Background/Aims: Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been reported to upregulate in urethral scar. However, the underlying molecular mechanisms remain undefined. Methods: Here, we studied levels of TIMP-1 and α-smooth muscle actin (α-SMA) in the fibroblasts isolated from urethral scar tissues, compared to the fibroblasts isolated from normal urethra. Then we either overexpressed TIMP-1, or inhibited TIMP-1 by lentiviruses carrying a transgene or a short hairpin small interfering RNA for TIMP-1 in human fibroblasts. We examined the effects of modulation of TIMP-1 on α-SMA, and on epithelial-mesenchymal transition (EMT)-related genes. We also studied the underlying mechanisms. Results: We detected significantly higher levels of TIMP-1 and α-smooth muscle actin (α-SMA) in the fibroblasts isolated from urethral scar tissues, compared to the fibroblasts isolated from normal urethra. Moreover, the levels of TIMP-1 and α-SMA strongly correlated. Moreover, we found that TIMP-1 significantly increased levels of α-SMA, transforming growth factor β 1 (TGFβ1), Collagen I and some other key factors related to an enhanced EMT, suggesting that TIMP-1 may induce transformation of fibroblasts into myofibroblasts to promote tissue EMT to enhance the formation of urethral scar. Moreover, increases in TIMP-1 also induced an increase in fibroblast cell growth and cell invasion, in an ERK/MAPK-signaling-dependent manner. Conclusion: Our study thus highlights a pivotal role of TIMP-1 in urethral scar formation.

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Section: Discussionmentioning

confidence: 96%

“…Thus efficient therapeutic interventions, e.g. inhibition of fibrosis, or decrease of collagen deposition, or increase of collagenolysis, are highly needed [5][6][7][8].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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TIMP-1 Induces α-Smooth Muscle Actin in Fibroblasts to Promote Urethral Scar Formation

et al. 2015

Cell Physiol Biochem

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“…In POP, it has been consistently demonstrated that the expression of MMP-2 is increased in uterosacral ligaments, and may be involved in altering collagen metabolism (44,45). Furthermore, TIMP-1 may regulate cellular processes including cell growth, apoptosis and differentiation, and may serve a role in urethral scar formation independent of its metalloproteinase inhibitory activity (38,46). At the genetic level, the TIMP-1 protein is encoded from six exons that may be functionally defined as an N-terminal domain (amino acids 1 to 126) that is sufficient to retain its inhibitory function of MMPs (47).…”

Section: Discussionmentioning

confidence: 99%

Effect of puerarin on collagen metabolism of fibroblasts in pelvic tissue of women with pelvic organ prolapse

Liu

et al. 2017

Mol Med Report

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The aim of the present study was to investigate the protective effect of puerarin on pelvic organ prolapse (POP) and the underlying mechanisms that regulate the metabolism of human parametrial ligament fibroblasts (HPLFs). HPLFs obtained from the pelvic tissue of patients with (n=10) or without (n=8) POP during hysterectomy were isolated by enzymatic digestion and subsequently identified by immunocytochemistry in a previous study of the authors. Following this, cultured HPLFs were treated with 0.01, 0.10 or 1.00 mmol/l puerarin, followed by detection of proliferation rate by Cell Counting kit‑8 assay. Following incubation with puerarin for 48 h, mRNA and protein expression levels of tissue inhibitor of metalloproteinase‑1 (TIMP‑1), matrix metalloproteinase (MMP)‑2 and ‑9, and collagen (COL)I and III in HPLFs were quantified by reverse transcription‑quantitative polymerase chain reaction, and western blot and gelatin zymography analyses, respectively. MMP‑2 and ‑9 expression levels were increased, whereas expression levels of TIMP‑1, and COL I and III were decreased, in patients with POP compared with healthy controls. Following puerarin treatment, the expression levels of TIMP‑1, and COL I and III were enhanced, whereas MMP‑2 and ‑9 were inhibited. In conclusion, the present study demonstrated evidence increased degradation of the extracellular matrix in pelvic tissues of patients with POP compared with controls, and the protective effect of puerarin against POP via its anti‑degradation effect on collagen. These results provide evidence for puerarin as a novel approach for the treatment of POP.

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“…In 2008, Korpal found that miR-200c can resist and reverse TGF-β1-induced EMT [14]. Another study confirmed that TGF-β1 has a vital role in the occurrence and development of urethral scar fibrosis [15]. Previously, Smad3 was found to be a downstream signal transduction factor of TGF-β1 [16].…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanism of MicroRNA-200c Regulating Transforming Growth Factor-β (TGF-β)/SMAD Family Member 3 (SMAD3) Pathway by Targeting Zinc Finger E-Box Binding Homeobox 1 (ZEB1) in Hypospadias in Rats

Qian¹,

Dang²,

Wang³

et al. 2016

Med Sci Monit

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BackgroundThe aim of this study was to explore effects of microRNA-200c regulating TGF-β/Smad3 pathway by targeting Zeb1 on the occurrence and development of hypospadias and to evaluate the relationship between microRNA-200c and occurrence of hypospadias.Material/MethodsPregnant rats with a gestational age of 12 days were allocated into 2 groups; one received gavage of DEHP-contained soybean oil (1 ml/day, 8 days; Group A) and the other had gavage of normal soybean oil (1 ml/day, 8 days; Group B). Baby rats with hypospadias from Group A were assigned to the model group (n=20) and healthy baby rats from Group B were assigned to the control group (n=20). Real-time quantitative polymerase chain reaction (qRT-PCR), immunohistochemistry and Western blot analysis were performed to detect microRNA-200c, Zeb1, TGF-β, and Smad3 mRNA and protein expressions in the model group (n=20) and the control group (n=20). The relationship between microRNA-200c and Zeb1 was detected using a dual-luciferase reporter gene experiment. After the in vitro intervention experiment in fetal rat penises, Western blot was used to detect the expression of Zeb1, TGF-β, and Smad3.ResultsIn the model group, microRNA-200c was expressed at a low level, and microRNA-200c expression in control group was 2.1 times higher than in the model group (P<0.05). When compared with the control group, mRNA expressions, protein expressions, and positive rates of Zeb1, TGF-β, and Smad3 were higher in the model group (all P<0.01). Luciferase gene report determined that Zeb1 is a target gene of microRNA-200c. The in vitro intervention experiment in fetal rat penises found that a high concentration of microRNA-200c inhibited hypospadias occurrence by suppressing the expression of Zeb1, TGF-β, and Smad3.ConclusionsMicroRNA-200c was expressed in hypospadias penis tissues at low levels and was negatively correlated with Zeb1 expression. MicroRNA-200c up-regulated Zeb1 expression to regulate the TGF-β/Smad3 pathway, which led to the occurrence of hypospadias.

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Preliminary experimental study of urethral reconstruction with tissue engineering and RNA interference techniques

Cited by 9 publications

References 23 publications

TIMP-1 Induces α-Smooth Muscle Actin in Fibroblasts to Promote Urethral Scar Formation

TIMP-1 Induces α-Smooth Muscle Actin in Fibroblasts to Promote Urethral Scar Formation

Effect of puerarin on collagen metabolism of fibroblasts in pelvic tissue of women with pelvic organ prolapse

Molecular Mechanism of MicroRNA-200c Regulating Transforming Growth Factor-β (TGF-β)/SMAD Family Member 3 (SMAD3) Pathway by Targeting Zinc Finger E-Box Binding Homeobox 1 (ZEB1) in Hypospadias in Rats

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