scholarly journals Mesenchymal stem cells ameliorate partial bladder outlet obstruction-induced epithelial-mesenchymal transition type II independent of mast cell recruitment and degranulation

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Rutuja Kadam ◽  
Bridget Wiafe ◽  
Peter D. Metcalfe
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Mechanism Of Action ◽  
Bladder Outlet Obstruction ◽  
Epithelial Mesenchymal Transition ◽  
Outlet Obstruction ◽  
Type Ii ◽  
Mesenchymal Transition ◽  
Cell Recruitment ◽  
Partial Bladder Outlet Obstruction

Introduction: Partial bladder outlet obstruction (pBOO) results in increased urinary storage pressure and significant morbidity. Increased pressure results in a sequence of programmed events: an initial inflammatory phase, smooth muscle hypertrophy, and fibrosis. Although epithelial-mesenchymal transition (EMT) and mast cell accumulation play intermediary roles in some fibrotic conditions, their role in pBOO has not yet been elucidated. Mesenchymal stem cell (MSC) therapy is emerging as a promising treatment for several conditions. It potently inhibits bladder deterioration after pBOO; however, its mechanism of action is insufficiently understood. Thus, we hypothesize that EMT type II pathway plays a significant role in pBOO, aided by the recruitment and activation of mast cells, and these are potently inhibited by MSCs. Methods: PBOO was surgically induced in female Sprague-Dawley rats and simultaneously treated with MSCs. Treatment effect was determined after two or four weeks, and compared to untreated controls. Immunohistochemistry was used to measure markers characteristic of EMT (vimentin, collagenase, and collagen). Whole and degranulated mast cell counts were also performed. Results: PBOO resulted in an increased expression of collagenase, vimentin, and collagen. Mast cell recruitment increased proportionately to the length of bladder obstruction. MSC treatment significantly mitigated the EMT type II response, but mast cell recruitment and degranulation were unaffected. Conclusions: Our results demonstrate the involvement of EMT type II in the pathophysiology of pBOO and confirm its mitigation with MSC treatment independent of mast cells response. The observations provide insight into the mechanism of action and have therapeutic ramifications.

1227: Effects of Short-Term Partial Bladder Outlet Obstruction on the Expression of Smooth Muscle Contractile and Regulatory Proteins

2005 ◽  
Vol 173 (4S) ◽  
pp. 333-333
Author(s):  
Shaohua Chang ◽  
Joseph A. Hypolite ◽  
Alan J. Wein ◽  
Samuel Chacko ◽  
Michael E. DiSanto
Keyword(s):  
Smooth Muscle ◽  
Bladder Outlet Obstruction ◽  
Outlet Obstruction ◽  
Regulatory Proteins ◽  
Short Term ◽  
Partial Bladder Outlet Obstruction ◽  
Muscle Contractile

1454: Protein Oxidation Following Partial Bladder Outlet Obstruction

2005 ◽  
Vol 173 (4S) ◽  
pp. 394-394
Author(s):  
Martha A. Hass ◽  
Robert M. Levin ◽  
William Connors ◽  
Alma Birnboim
Keyword(s):  
Protein Oxidation ◽  
Bladder Outlet Obstruction ◽  
Outlet Obstruction ◽  
Partial Bladder Outlet Obstruction

scholarly journals Human umbilical cord mesenchymal stem cell-derived exosomal miR-27b attenuates subretinal fibrosis via suppressing epithelial–mesenchymal transition by targeting HOXC6

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dongli Li ◽  
Junxiu Zhang ◽  
Zijia Liu ◽  
Yuanyuan Gong ◽  
Zhi Zheng
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Umbilical Cord ◽  
Mechanism Of Action ◽  
Epithelial Mesenchymal Transition ◽  
Human Umbilical Cord ◽  
Mesenchymal Transition ◽  
Rpe Cells ◽  
Subretinal Fibrosis

Abstract Background and aim Subretinal fibrosis resulting from neovascular age-related macular degeneration (nAMD) is one of the major causes of serious and irreversible vision loss worldwide, and no definite and effective treatment exists currently. Retinal pigmented epithelium (RPE) cells are crucial in maintaining the visual function of normal eyes and its epithelial–mesenchymal transition (EMT) is associated with the pathogenesis of subretinal fibrosis. Stem cell-derived exosomes have been reported to play a crucial role in tissue fibrosis by transferring their molecular contents. This study aimed to explore the effects of human umbilical cord-derived mesenchymal stem cell exosomes (hucMSC-Exo) on subretinal fibrosis in vivo and in vitro and to investigate the anti-fibrotic mechanism of action of hucMSC-Exo. Methods In this study, human umbilical cord-derived mesenchymal stem cells (hucMSCs) were successfully cultured and identified, and exosomes were isolated from the supernatant by ultracentrifugation. A laser-induced choroidal neovascularization (CNV) and subretinal fibrosis model indicated that the intravitreal administration of hucMSC-Exo effectively alleviated subretinal fibrosis in vivo. Furthermore, hucMSC-Exo could efficaciously suppress the migration of retinal pigmented epithelial (RPE) cells and promote the mesenchymal–epithelial transition by delivering miR-27b-3p. The latent binding of miR-27b-3p to homeobox protein Hox-C6 (HOXC6) was analyzed by bioinformatics prediction and luciferase reporter assays. Results This study showed that the intravitreal injection of hucMSC-Exo effectively ameliorated laser-induced CNV and subretinal fibrosis via the suppression of epithelial–mesenchymal transition (EMT) process. In addition, hucMSC-Exo containing miR-27b repressed the EMT process in RPE cells induced by transforming growth factor-beta2 (TGF-β2) via inhibiting HOXC6 expression. Conclusions The present study showed that HucMSC-derived exosomal miR-27b could reverse the process of EMT induced by TGF-β2 via inhibiting HOXC6, indicating that the exosomal miR-27b/HOXC6 axis might play a vital role in ameliorating subretinal fibrosis. The present study proposed a promising therapeutic agent for treating ocular fibrotic diseases and provided insights into the mechanism of action of hucMSC-Exo on subretinal fibrosis.

Altered Cavernosal Endothelin-B-Receptor Binding Sites in the Rabbit Model of Partial Bladder Outlet Obstruction

2000 ◽  
Vol 36 ◽  
pp. S260-S261
Author(s):  
Cecil S. Thompson ◽  
Masood A. Khan ◽  
Michael R. Dashwood ◽  
Faiz H. Mumtaz ◽  
Dimitri P. Mikhailidis ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Binding Sites ◽  
Bladder Outlet Obstruction ◽  
Rabbit Model ◽  
Outlet Obstruction ◽  
Endothelin B Receptor ◽  
Partial Bladder Outlet Obstruction ◽  
Endothelin B

Partial Bladder Outlet Obstruction in Mice May Cause E-Cadherin Repression through Hypoxia Induced Pathway

2014 ◽  
Vol 192 (3) ◽  
pp. 964-972 ◽  
Author(s):  
Naoko Iguchi ◽  
Amy Hou ◽  
Hari K. Koul ◽  
Duncan T. Wilcox
Keyword(s):  
Bladder Outlet Obstruction ◽  
Outlet Obstruction ◽  
Partial Bladder Outlet Obstruction ◽  
E Cadherin

scholarly journals Runx3 is a key modulator during the epithelial-mesenchymal transition of alveolar type II cells in animal models of BPD

2017 ◽  
Vol 40 (5) ◽  
pp. 1466-1476 ◽  
Author(s):  
Haiping Yang ◽  
Jianhua Fu ◽  
Li Yao ◽  
Ana Hou ◽  
Xindong Xue
Keyword(s):  
Animal Models ◽  
Epithelial Mesenchymal Transition ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Type Ii Cells ◽  
Mesenchymal Transition

scholarly journals Pathological Study on Epithelial-Mesenchymal Transition in Silicotic Lung Lesions in Rat

2019 ◽  
Vol 6 (3) ◽  
pp. 70 ◽  
Author(s):  
Mao Komai ◽  
Karin Mihira ◽  
Akinori Shimada ◽  
Ikumi Miyamoto ◽  
Kikumi Ogihara ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Pulmonary Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Crystalline Silicon ◽  
Interstitial Fibrosis ◽  
Female Rats ◽  
Dependent Manner ◽  
Type Ii ◽  
Mesenchymal Transition ◽  
Spindle Cells

Silicosis, caused by the inhalation of crystalline silicon dioxide or silica, is one of the most severe occupational diseases. Persistent inflammation and progressive massive pulmonary fibrosis are the most common histological changes caused by silicosis. Association of epithelial-mesenchymal transition (EMT) of hyperplastic type II epithelial cells with the fibrotic events of pulmonary fibrosis has been suggested in in vitro silica-exposed cultured cell models, patients with idiopathic pulmonary fibrosis, and bleomycin-induced experimental models. Histological features of EMT, however, are not fully described in silicotic lungs in in vivo. The purpose of this study was to demonstrate EMT of hyperplastic type II epithelial cells in the developmental process of progressive massive pulmonary fibrosis in the lungs of rats exposed to silica. F344 female rats were intratracheally instilled with 20 mg of crystalline silica (Min-U-Sil-5), followed by sacrifice at 1, 3, 6, and 12 months after instillation. Fibrosis, characterized by the formation of silicotic nodules, progressive massive fibrosis, and diffuse interstitial fibrosis, was observed in the lungs of the treated rats; the effects of fibrosis intensified in a time-dependent manner. Hyperplasia of the type II epithelial cells, observed in the massive fibrotic lesions, dominated in the lungs of rats at 6 and 12 months after the treatment. Immunohistochemistry of the serial sections of the lung tissues demonstrated positive labeling for cytokeratin, vimentin, and α-smooth muscle actin in spindle cells close to the foci of hyperplasia of type II epithelial cells. Spindle cells, which exhibited features of both epithelial cells and fibroblasts, were also demonstrated with bundles of collagen fibers in the fibrotic lesions, using electron microscopy. Increased expression of TGF-β was shown by Western blotting and immunohistochemistry in the lungs of the treated rats. These findings suggested that enhanced TGF-β expression and EMT of hyperplastic type II epithelial cells are involved in the development process of progressive massive pulmonary fibrosis during silicosis.

scholarly journals Human Urine-derived Stem Cells Improve Partial Bladder Outlet Obstruction in Rats: Preliminary Data and microRNA-mRNA Expression Profile

2021 ◽  
Author(s):  
Menjiang Tu ◽  
Rui Wang ◽  
Pei Zhu ◽  
Qingqing Wang ◽  
Bishao Sun ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Bladder Outlet Obstruction ◽  
Bioinformatics Analysis ◽  
Therapy Group ◽  
Expression Profiles ◽  
Outlet Obstruction ◽  
Bladder Function ◽  
Detrusor Muscle ◽  
Bladder Tissue ◽  
Partial Bladder Outlet Obstruction

Abstract Background: Partial bladder outlet obstruction (pBOO), a common urological disease, often results in bladder tissue inflammation and remodeling. Human urine-derived stem cells (USCs) have demonstrated therapeutic benefits in various organ injury models. We used a rat model of pBOO to investigate the effect of USCs on bladder function and to explore the miRNA and gene expression profiles in bladder tissue using RNA sequencing.Methods: In total, 18 rats were randomly and evenly assigned to the following three groups: a sham surgery group, a pBOO without USC therapy group, and a pBOO with USC therapy group (subjected to treatment with USCs six times every other week). All rats were subjected to routine urodynamic monitoring. Detrusor muscle strips were analyzed and pathophysiology was assessed. Finally, altered miRNA and mRNA expression profiles of bladder tissue were examined using RNA sequencing and bioinformatics analysis technology.Results: After USC treatment, urodynamic monitoring revealed elevated bladder compliance and maximal voiding pressure, declined end filling pressure and voided volume, and improved detrusor muscle contractility and carbachol sensitivity in pBOO rats. Histology and TUNEL assay revealed reduced collagen deposition and muscle cell apoptosis in bladder tissue. The differential expression of eight miRNAs in pBOO rats was reversed by USC treatment. Bioinformatics analysis helped identify miR-142 and miR-9a as the two largest nodes of differentially expressed miRNAs in the miRNA‑gene interaction network in the USC-treated group. The Kyoto Encyclopedia of Genes and Genomes analysis revealed enrichment of multiple significant pathways, including those involved in necroptosis and cytokine-cytokine receptor interactions.Conclusions: This is the first study to reveal the protective effect of USCs on bladder function and bladder remodeling in pBOO rats. The miRNA and mRNA expression levels differed in the bladder of pBOO rats with and without USC treatment. Although the mechanism underlying these effects has not been fully elucidated, necroptosis and cytokine-cytokine receptor interaction-related pathways may be involved.

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