Prostatic epithelial cells and their high expressions of CKIP-1 affect the TGF-β1 expression levels which might reduce the scar formation in remodeling stage at prostatic urethral wounds after wound repair

Abstract Objective There are less scar formations in some wounds after wound repair. Our earlier study had shown that the amount of collagen fibers in canine prostatic urethra wound were less than in bladder neck wound after 2-μm laser resection of the prostate (TmLRP) and partial bladder neck mucosa at 4 weeks. The purpose of this study was to observe the amount of scar tissue and characterize the probable causes of “less scar healing” in prostatic urethra wound. Methods A total of 12 healthy adult male crossbred canines underwent resection of prostate and partial bladder neck mucosa using 2-μm laser. The prostatic urethra and bladder neck wound specimens were harvested at 3, 4, 8 and 12 weeks after operation, respectively. The histopathologic characteristics were observed by hematoxylin and eosin(HE)staining, and the expression of transforming growth factor-β1 (TGF-β1) and casein kinase-2 interacting protein-1 (CKIP-1) were examined by immunohistochemistry in prostatic urethra and bladder neck wound, respectively. Overexpressed CKIP-1 human prostate epithelial cells (BPH-1 cells) were established and the expression of TGF-β1 was detected by Western blotting. Furthermore, a non-contact co-culture system of BPH-1 cells and human fibroblast (HFF-1) cells was used to observe the effects of BPH-1 cell and their high CKIP-1 levels on the expression of TGF-β1 in HFF-1 in vitro. Results The histology showed that there were a large number of prostatic epithelium and a small amount of scar tissue in prostatic urethra wound, while no epithelial cells and more scar tissue in bladder neck wound at 4, 8 and 12 weeks after repair. There were a higher expression level of TGF-β1 in prostate epithelial cells and fibroblasts and a lower expression level of CKIP-1 in prostate epithelial cells at 3 weeks after surgery in prostatic urethral wound. Compared to week 3, the TGF-β1 expression decreased both in prostate epithelial cells and fibroblasts at 4, 8 and 12 weeks in prostatic urethral wound (p < 0.05 or p < 0.01). The CKIP-1 expression increased in prostate epithelial cells at 4, 8 and 12 weeks compared to 3 weeks in prostatic urethra wound (p < 0.01). A higher TGF-β1 expression level of fibroblasts was observed in bladder neck wound at 3 weeks. And there was no significant change in the expression of TGF-β1 of fibroblasts in 3, 4, 8 and 12 weeks after operation in bladder neck wound. Both the prostate urethra and bladder neck wound fibroblasts showed weak expression of CKIP-1 and there was no significant change in 3, 4, 8 and 12 weeks. The vitro experiments showed that the TGF-β1 expression in BPH-1 cells with CKIP-1 overexpression decreased 25% compared with control group (p < 0.05). Furthermore, the expression of TGF-β1 in HFF-1 cells of co-cultured group decreased by 20% compared with Control group (p < 0.05); the expression of TGF-β1 in HFF-1 cells of overexpression co-culture group were reduced by 15% compared with co-cultured group (p < 0.01). Conclusions A large number of prostate epithelial cells in prostatic urethra wound may be one of the causes of less formation of scar tissue after repair. The prostate epithelial cells might reduce expression level of TGF-β1 by raising CKIP-1 expression and inhibit expression of TGF-β1 in peripheral fibroblasts at remodeling stage to reduce the excessive proliferation of fibrous cells and the excessive scar formation.

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Urine can speed up the re-epithelialization process of prostatic urethra wounds by promoting the proliferation and migration of prostate epithelial cells

International Urology and Nephrology ◽

10.1007/s11255-018-2019-2 ◽

2018 ◽

Vol 51 (1) ◽

pp. 9-15 ◽

Cited By ~ 1

Author(s):

Lixin Wang ◽

Ying Cao ◽

Ye Tian ◽

Guangheng Luo ◽

Xiushu Yang ◽

...

Keyword(s):

Epithelial Cells ◽

Prostatic Urethra ◽

Prostate Epithelial Cells ◽

Speed Up ◽

And Migration ◽

Proliferation And Migration

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A two staged treatment procedure for the difficult to treat bladder neck contractures with concomitant incontinence. In the search of a solution to a complex problem

Archivio Italiano di Urologia e Andrologia ◽

10.4081/aiua.2015.3.233 ◽

2015 ◽

Vol 87 (3) ◽

pp. 233

Author(s):

Ioannis Adamakis ◽

Evangelos Fragkiadis ◽

Ioannis Katafigiotis ◽

Giorgos Kousournas ◽

Konstantinos Stravodimos ◽

...

Keyword(s):

Transurethral Resection ◽

Bladder Neck ◽

Scar Tissue ◽

Complex Problem ◽

Control Group ◽

Artificial Sphincter ◽

Number Of Patients ◽

Fibrotic Scar ◽

Staged Treatment

Objective: To examine the efficacy of a two staged treating strategy with the use of a non-permanent urethral ALLIUM® stent for the management of recurrent bladder neck stenosis and subsequently the use of an artificial sphincter AUS800® by AMS for the management of the incontinence. Materials and Methods: We progressively identified patients eligible for the study creating a population of cases with recurrent bladder neck stenosis and concomitant incontinence occurring after the last intervention for the stenosis. Efficacy for the treatment of the stenosis was defined as no recurrence both prior and post to the sphincter placement and efficacy for the treatment of the incontinence was defined as continence (0-1pads) after the sphincter placement. Results and Limitations: 14 white males with a mean age of 66.21, ranging from 59 to 73 years consisted the population of the study. All patients had severe stress incontinence following the last transurethral resection. The efficacy of the treatment of the bladder neck stenosis was 93% (13/14) while the efficacy for the treatment of the incontinence was 100%. A single patient had a recurrent bladder neck stenosis after the artificial sphincter placement and was treated with transurethral resection using a long pediatric 13 F resectoscope at 12 months. Our limitations is the absence of a control group and the small number of patients enrolled, with a relatively short time of follow up. Conclusions: In our series we propose the use of a non-permanent urethral ALLIUM® stent for 6 months in order to control the growth of fibrotic scar tissue, a further 6 months follow up for recurrence, and then placement of an artificial sphincter. The results are very promising both on stabilizing the vesicourethral stenosis, and on patient safety and tolerability.

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Mechanism of lipopolysaccharide-mediated induction of epithelial-mesenchymal transition of alveolar type II epithelial cells in absence of other inflammatory cells

European Journal of Inflammation ◽

10.1177/20587392211014427 ◽

2021 ◽

Vol 19 ◽

pp. 205873922110144

Author(s):

Shuai Wu ◽

Huan Ye ◽

TianJiao Xue ◽

Jiali Wang

Keyword(s):

Epithelial Cells ◽

Pulmonary Fibrosis ◽

Epithelial Mesenchymal Transition ◽

Mesenchymal Cell ◽

Expression Level ◽

Alveolar Type ◽

Type Ii ◽

Gram Negative ◽

Mesenchymal Transition ◽

Tgf Β1

Several studies have shown that gram-negative bacilli infection can cause acute lung injury, and that consequent pulmonary fibrosis is caused when alveolar type-II epithelial cells undergo epithelial-mesenchymal transition (EMT). However, the mechanism underlying this change remains unclear. This study aimed to elucidate whether the main toxin of gram-negative bacteria, lipopolysaccharide (LPS), can induce EMT in human alveolar epithelial cells, and the underlying molecular mechanisms. Human alveolar type-II epithelial cells (A549) were used in EMT induction experiments. Cells were collected after LPS exposure, and changes in the expression levels of epithelial and mesenchymal cell markers were determined. Further, the effect of LPS exposure on the expression of Toll-like Receptor 4 (TLR4), Transforming Growth Factor-beta 1 (TGF-β1) and Smad2/3 was assessed. The expression level of a mesenchymal cell marker was also assessed after pharmacological inhibition of TLR4 and TGF-β1 prior to addition of LPS, to identify downstream pathways involved in EMT induction. Results showed that LPS exposure caused significant downregulation of epithelial marker E-cadherin, and upregulation of mesenchymal marker vimentin, together with increased expression of TGF-β1 and activation of the TGF-β1/Smad2/3 pathway. Furthermore, pretreatment with TGF-β1 and TLR4 inhibitors suppressed EMT, and treatment with the latter also reduced the expression level of TGF-β1. Overall, we conclude that LPS directly induces EMT in A549 cells through upregulation of TLR4 and activation of the TGF-β1/Smad2/3 signalling pathway. Our results suggest that LPS-mediated pulmonary fibrosis may occur in ALI patients even if the LPS-induced inflammatory response is inhibited.

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TGF-β1 signaling plays a dominant role in the crosstalk between TGF-β1 and the aryl hydrocarbon receptor ligand in prostate epithelial cells

Cellular Signalling ◽

10.1016/j.cellsig.2012.04.008 ◽

2012 ◽

Vol 24 (8) ◽

pp. 1665-1676 ◽

Cited By ~ 15

Author(s):

Andrea Staršíchová ◽

Eva Hrubá ◽

Eva Slabáková ◽

Zuzana Pernicová ◽

Jiřina Procházková ◽

...

Keyword(s):

Epithelial Cells ◽

Aryl Hydrocarbon Receptor ◽

Dominant Role ◽

Receptor Ligand ◽

Aryl Hydrocarbon Receptor Ligand ◽

Aryl Hydrocarbon ◽

Prostate Epithelial Cells ◽

Tgf Β1

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DNMT1 regulates IL-6- and TGF-β1-induced epithelial mesenchymal transition in prostate epithelial cells

European Journal of Histochemistry ◽

10.4081/ejh.2017.2775 ◽

2017 ◽

Cited By ~ 7

Author(s):

Hui Xu ◽

Yanbo Chen ◽

Qi Chen ◽

Huan Xu ◽

Yanxia Wang ◽

...

Keyword(s):

Epithelial Cells ◽

Promoter Region ◽

Epithelial Mesenchymal Transition ◽

Inflammatory Factors ◽

Dna Hypermethylation ◽

Normal Prostate ◽

Mesenchymal Transition ◽

Prostate Epithelial Cells ◽

Tgf Β1 ◽

E Cadherin

Multiple factors have been considered to play a role in the development of benign prostatic hyperplasia (BPH), including chronic inflammation, hormones, and epithelial-mesenchymal transition (EMT). Inflammation is regarded as one of the potential inducers of EMT. However, the mechanisms, modulating pro-inflammatory factors (IL-6 and TGF-β1) induce EMT features, have not yet been studied in BPH. In this study, we investigated whether DNA methyltransferases1 (DNMT1) could regulate IL-6 and TGF-β1 induce EMT. The expression of EMT features was analyzed in normal prostate epithelial cells (PrECs) and BPH1 cells. Real-time RT-PCR and western blotting were used to examine the expression of EMT features in IL-6- and TGF-β1-treated PrECs. Next, bisulfite sequencing PCR (BSP) methods were used to examine the DNA methylation level of the Cdh1 promoter region. The results showed that EMT features were increased in BPH1 cells, compared to PrECs. IL-6 and TGF-β1 treatment induced EMT features, including decreased E-cadherin expression. The results of BSP revealed significant DNA hypermethylation at the promoter region of Cdh1 after IL-6 and TGF-β1 exposure, which was rescued when pretreated with 5-Aza or TGF-β1 antibody. Moreover, the protein expression and methyltransferase activity of DNMT1 were also increased after IL-6 and TGF-β1 induction. Collectively, our study showed that IL-6 and TGF-β1 could activate DNMT1 and directly regulate the expression of E-cadherin in PrECs, providing a potential therapeutic candidate for BPH.

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Transforming growth factor-β1 increases airway wound repair via MMP-2 upregulation: a new pathway for epithelial wound repair?

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00149.2005 ◽

2006 ◽

Vol 290 (6) ◽

pp. L1277-L1282 ◽

Cited By ~ 34

Author(s):

E. Lechapt-Zalcman ◽

V. Prulière-Escabasse ◽

D. Advenier ◽

S. Galiacy ◽

C. Charrière-Bertrand ◽

...

Keyword(s):

Growth Factor ◽

Epithelial Cells ◽

Wound Repair ◽

Transforming Growth Factor ◽

Airway Epithelial ◽

Airway Injury ◽

Tgf Β1

In vivo, transforming growth factor (TGF)-β1 and matrix metalloproteinases (MMPs) present at the site of airway injury are thought to contribute to epithelial wound repair. As TGF-β1 can modulate MMP expression and MMPs play an important role in wound repair, we hypothesized that TGF-β1 may enhance airway epithelial repair via MMPs secreted by epithelial cells. We evaluated the in vitro influence of TGF-β1 on wound repair in human airway epithelial cells cultured under conditions allowing differentiation. The results showed that TGF-β1 accelerated in vitro airway wound repair, whereas MMP inhibitors prevented this acceleration. In parallel, we examined the effect of TGF-β1 on the expression of MMP-2 and MMP-9. TGF-β1 induced a dramatic increase of MMP-2 expression with an increased steady-state level of MMP-2 mRNA, contrasting with a slight increase in MMP-9 expression. To confirm the role of MMP-2, we subsequently evaluated the effect of MMP-2 on in vitro airway wound repair and demonstrated that the addition of MMP-2 reproduced the acceleration of wound repair induced by TGF-β1. These results strongly suggest that TGF-β1 increases in vitro airway wound repair via MMP-2 upregulation. It also raises the issue of a different in vivo biological role of MMP-2 and MMP-9 depending on the cytokine microenvironment.

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Id-1 promotes TGF-β1-induced cell motility through HSP27 activation and disassembly of adherens junction in prostate epithelial cells

Experimental Cell Research ◽

10.1016/j.yexcr.2007.08.023 ◽

2007 ◽

Vol 313 (19) ◽

pp. 3983-3999 ◽

Cited By ~ 21

Author(s):

Kaijun Di ◽

Yong Chuan Wong ◽

Xianghong Wang

Keyword(s):

Epithelial Cells ◽

Cell Motility ◽

Adherens Junction ◽

Prostate Epithelial Cells ◽

Tgf Β1

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Exposure of Prostate to Lipopolysaccharide and Hypoxia Potentiates Neoplastic Behavior and Risk for Prostate Carcinogenesis In Vivo

International Scholarly Research Notices ◽

10.1155/2014/420429 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Maxwell Omabe ◽

Kenneth Omabe ◽

Martin Okwuegbu ◽

Ogo Grace ◽

Desmond Uchenna Okoro

Keyword(s):

Prostate Cancer ◽

Epithelial Cells ◽

Test Group ◽

Fold Increase ◽

High Rate ◽

Control Group ◽

Stress Injury ◽

E Coli ◽

Prostate Epithelial Cells

A number of studies showed that men from tropical countries have higher burden of prostate cancer similar to data from USA. We developed a translational model to examine whether exposure to microbial inflammation-inducing molecule lipopolysacchride LPS was associated with prostatic cell transformation to more proliferative phenotype as indicated by PSA secretion. Immunocompetent adult mice were divided into two groups; the first group received a local prostate inoculation with E. coli, while the second group received inoculation with sterile solution of saline as vehicle. At the end of 6 days, the PSA values were measured and compared. In the second experiment, two groups of animals were involved. The test group received two drops of the hydrogen peroxide orally for six to seven days to induce hypoxia, while the control group received normal saline. Blood samples were evaluated for serum level of PSA. Result showed a 2-fold increase in level of PSA compared to the control mice in the E. coli inoculated-LPS exposed animals. In addition, exposure of the animals to hypoxic stress resulted in 3.5 fold increase in the serum PSA compared to the control group, which was found to be statistically significant (P<0.0001). In conclusion, our data shows that chronic prostatic infection and exposure to inflammatory stimulus, especially LPS, may alter the phenotype of prostate epithelial cells for increased PSA secretion, a known cancer-like behavior; this is mediated by compromised redox state and oxidative stress injury. We propose that exposure of the prostate epithelial cells to lipopolysaccharide (LPS) promotes chronic inflammation and risk of neoplastic behavior of the prostate in vivo; this may explain the high rate of prostate cancer in tropics.

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