Changes in human bladder epithelial cell gene expression associated with interstitial cystitis or antiproliferative factor treatment

2003 ◽  
Vol 14 (2) ◽  
pp. 107-115 ◽  
Author(s):  
Susan Keay ◽  
Francoise Seillier-Moiseiwitsch ◽  
Chen-Ou Zhang ◽  
Toby C. Chai ◽  
Jialu Zhang
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Interstitial Cystitis ◽  
Expression Patterns ◽  
Epithelial Cell Proliferation ◽  
Normal Cells ◽  
Bladder Epithelial Cell ◽  
Normal Bladder

Explanted bladder epithelial cells from patients with interstitial cystitis (IC) have been shown to differ from explanted control cells in several ways, including production of an antiproliferative factor (APF), altered production of certain epithelial growth factors, and rate of proliferation. To better understand the role of the APF in abnormal bladder epithelial cell proliferation in IC, we studied gene expression patterns in normal bladder epithelial cells treated with APF vs. mock APF and compared them to expression patterns in IC vs. normal cells using microarray analysis. Oligo-dT-primed total cellular RNA was labeled with [33P]dCTP and hybridized to GeneFilter GF211 microarray membranes (Research Genetics) containing cDNA for 3,964 human genes. Thirteen genes that function in epithelial cell proliferation or differentiation were consistently differentially expressed in both IC (compared with control) and APF-treated (compared with mock APF-treated) normal bladder epithelial cells. The general pattern of gene expression in IC and APF-treated cells suggested a less proliferative phenotype, with increased expression of E-cadherin, phosphoribosylpyrophosphate synthetase-associated protein 39, and SWI/SNF complex 170-kDa subunit, and decreased expression of vimentin, α2-integrin, α1-catenin, cyclin D1, and jun N-terminal kinase 1; these findings were confirmed for the structural gene products (E-cadherin, vimentin, α2-integrin, and α-catenin) by immunohistochemistry. These results are compatible with the previously noted decreased proliferation rate of IC and APF-treated normal cells, and indicate that the mechanism whereby APF inhibits cell proliferation may involve both downregulation of genes that stimulate cell proliferation along with upregulation of genes that inhibit cell growth.

Estrogen-dependent responses of the mammary fat pad in prepubertal dairy heifers

2006 ◽  
Vol 190 (3) ◽  
pp. 819-827 ◽  
Author(s):  
M J Meyer ◽  
A V Capuco ◽  
Y R Boisclair ◽  
M E Van Amburgh
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Epithelial Cell Proliferation ◽  
Fat Pad ◽  
Dairy Heifers ◽  
Ovarian Status ◽  
Mammary Fat Pad ◽  
Igf I

Ovaries are absolutely required for development of the mammary parenchyma (PAR) in cattle, reflecting estrogen-dependent epithelial cell proliferation. However, the estrogen receptor (ER) that mediates the mammary estrogen effects, ERα, is absent in proliferating epithelial cells. In the mouse, this discrepancy is explained in part by the ability of the mammary fat pad (MFP) to synthesize epithelial cell mitogens such as IGF-I in response to estrogen. Consistent with a similar role for the bovine MFP, 30% of its fibroblasts and adipocytes were immunoreactive for ERα in prepubertal dairy heifers. To assess estrogen-dependent gene expression in the MFP, 16 prepubertal dairy heifers were randomly assigned to a 2×2 factorial. The first factor was ovarian status, with heifers undergoing bilateral ovariectomy or left intact at 4.6 months of age. The second factor was applied 30 days after surgery and consisted of injection of estrogen or excipient. After 3 days of injection, heifers were administered an intrajugular bolus of bromodeoxyuridine (BrdU) and slaughtered 2 h later. The estrogen injection, but not ovarian status, caused significant increases in the fraction of epithelial cells labeled with BrdU and produced tissue-specific effects on gene expression. In the PAR, estrogen injection increased IGF-I gene expression by twofold despite reductions of 50% or more in ERα mRNA abundance and the fraction of epithelial cells immunoreactive for ERα. The estrogen-dependent increase in IGF-I mRNA was greater in the MFP, presumably because estrogen failed to downregulate ERα expression in this mammary compartment. Finally, estrogen-responsiveness of the MFP appears unique among the bovine fat depots as estrogen injection did not induce IGF-I expression in its s.c. counterpart. Our data demonstrate that the bovine MFP is highly responsive to exogenous estrogen, consistent with a role for this tissue compartment in communicating its effects on epithelial cell proliferation.

scholarly journals c-Src inactivation reduces renal epithelial cell-matrix adhesion, proliferation, and cyst formation

2011 ◽  
Vol 301 (2) ◽  
pp. C522-C529 ◽  
Author(s):  
Justine Elliott ◽  
Nadezhda N. Zheleznova ◽  
Patricia D. Wilson
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Collecting Duct ◽  
Specific Inhibitor ◽  
Cell Phenotype ◽  
Epithelial Cell Proliferation ◽  
Matrix Adhesion ◽  
Cyst Lining

c-Src is a non-receptor tyrosine kinase whose activity is induced by phosphorylation at Y418 and translocation from the cytoplasm to the cell membrane. Increased activity of c-Src has been associated with cell proliferation, matrix adhesion, motility, and apoptosis in tumors. Immunohistochemistry suggested that activated (pY418)-Src activity is increased in cyst-lining autosomal dominant polycystic kidney disease (ADPKD) epithelial cells in human and mouse ADPKD. Western blot analysis showed that SKI-606 (Wyeth) is a specific inhibitor of pY418-Src without demonstrable effects on epidermal growth factor receptor or ErbB2 activity in renal epithelia. In vitro studies on mouse inner medullary collecting duct (mIMCD) cells and human ADPKD cyst-lining epithelial cells showed that SKI-606 inhibited epithelial cell proliferation over a 24-h time frame. In addition, SKI-606 treatment caused a striking statistically significant decrease in adhesion of mIMCD and human ADPKD to extracellular collagen matrix. Retained viability of unattached cells was consistent with a primary effect on epithelial cell anchorage dependence mediated by the loss of extracellular matrix (ECM)-attachment due to α2β1-integrin function. SKI-606-mediated attenuation of the human ADPKD hyperproliferative and hyper-ECM-adhesive epithelial cell phenotype in vitro was paralleled by retardation of the renal cystic phenotype of Pkd1 orthologous ADPKD heterozygous mice in vivo. This suggests that SKI-606 has dual effects on cystic epithelial cell proliferation and ECM adhesion and may have therapeutic potential for ADPKD patients.

scholarly journals Dihydroartemisinin Ameliorates Chronic Nonbacterial Prostatitis and Epithelial Cellular Inflammation by Blocking the E2F7/HIF1α Pathway

2021 ◽  
Author(s):  
Yan Zhou ◽  
Jun-hao Wang ◽  
Jian-peng Han ◽  
Jian-yong Feng ◽  
Kuo Guo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Inflammatory Response ◽  
Inflammatory Factors ◽  
Protective Effects ◽  
Epithelial Cell Proliferation ◽  
Chronic Nonbacterial Prostatitis ◽  
Cellular Inflammatory Response ◽  
Nonbacterial Prostatitis

Abstract Objective: Chronic nonbacterial prostatitis (CNP) has remained one of the most prevalent urological diseases, particularly in older men. Dihydroartemisinin (DHA) has been identified as a semi-synthetic derivative of artemisinin that exhibits broad protective effects. However, the role of DHA in inhibiting CNP inflammation and prostatic epithelial cell proliferation remains largely unknown. Materials and Methods: CNP mice model was induced by carrageenan and Haemotoxylin Eosin (HE) ,immunofluorescence and immunochemistry staining were used to confirm CNP and E2F7 expression. Human prostatic epithelial cells (HPECs) and RWPE-1 was induced by lipopolysaccharide (LPS) to mimic CNP model in vitro. Real-time quantitative PCR and Western blot were used to detect proliferation and inflammatory genes expression. Cell proliferation was determined using MTT assay.Results: DHA significantly alleviated the rough epithelium and inhibited multilamellar cell formation in the prostatic gland cavity and prostatic index induced by carrageenan. In addition, DHA decreased the expression of TNF-α and IL-6 inflammatory factors in prostatitis tissues and in LPS-induced epithelial cells. Upregulation of transcription factor E2F7, which expression was inhibited by DHA, was found in CNP tissues, human BPH tissues and LPS-induced epithelial cells inflammatory response. Mechanically, we found that depletion of E2F7 by shRNA inhibited epithelial cell proliferation and LPS-induced inflammation while DHA further enhance these effects. Furthermore, HIF1α was transcriptional regulated by E2F7 and involved in E2F7-inhibited CNP and cellular inflammatory response. Interestingly, we found that inhibition of HIF1α blocks E2F7-induced cell inflammatory response but does not obstruct E2F7-promoted cell growth.Conclusion: The results revealed that DHA inhibits the CNP and inflammation by blocking the E2F7/HIF1α pathway. Our findings provide new evidence for the mechanism of DHA and its key role in CNP, which may provide an alternative solution for the prevention and treatment of CNP.

Transcription factor NF-κB participates in regulation of epithelial cell turnover in the colon

2000 ◽  
Vol 279 (6) ◽  
pp. G1282-G1291 ◽  
Author(s):  
Mehmet Sait Inan ◽  
Veronica Tolmacheva ◽  
Qiang-Shu Wang ◽  
Daniel W. Rosenberg ◽  
Charles Giardina
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Transcription Factor ◽  
Epithelial Cell ◽  
Dna Binding ◽  
Epithelial Cells ◽  
Knockout Mice ◽  
Nuclear Antigen ◽  
Cell Turnover ◽  
Tnf Α

The transcription factor nuclear factor (NF)-κB regulates the expression of genes that can influence cell proliferation and death. Here we analyze the contribution of NF-κB to the regulation of epithelial cell turnover in the colon. Immunohistochemical, immunoblot, and DNA binding analyses indicate that NF-κB complexes change as colonocytes mature: p65-p50 complexes predominate in proliferating epithelial cells of the colon, whereas the p50-p50 dimer is prevalent in mature epithelial cells. NF-κB1 (p50) knockout mice were used to study the role of NF-κB in regulating epithelial cell turnover. Knockout animals lacked detectable NF-κB DNA binding activity in isolated epithelial cells and had significantly longer crypts with a more extensive proliferative zone than their wild-type counterparts (as determined by proliferating cell nuclear antigen staining and in vivo bromodeoxyuridine labeling). Gene expression profiling reveals that the NF-κB1 knockout mice express the potentially growth-enhancing tumor necrosis factor (TNF)-α and nerve growth factor-α genes at elevated levels, with in situ hybridization localizing some of the TNF-α expression to epithelial cells. TNF-α is NF-κB regulated, and its upregulation in NF-κB1 knockouts may result from an alleviation of p50-p50 repression. NF-κB complexes may therefore influence cell proliferation in the colon through their ability to selectively activate and/or repress gene expression.

412. The role of macrophages in regulating uterine epithelial cell proliferation

2008 ◽  
Vol 20 (9) ◽  
pp. 92
Author(s):  
A. S. Care ◽  
W. V. Ingman ◽  
M. J. Jasper ◽  
SA Robertson
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Diphtheria Toxin ◽  
Functional Markers ◽  
Epithelial Cell Proliferation ◽  
Uterine Epithelial Cells ◽  
Uterine Epithelial Cell ◽  
Macrophage Depletion ◽  
Embryo Attachment

During the oestrous cycle, uterine epithelial cells respond to ovarian steroid hormones by producing an array of cytokines and chemokines that cause macrophage recruitment into the uterus and regulate macrophage activation phenotype. In turn, growth factors and cytokines synthesised by macrophages potentially impact epithelial cell proliferation, secretory function and receptivity to embryo attachment. To investigate the hypothesis that uterine macrophages are essential contributors to the proliferation of uterine epithelial cells, we have used an ovariectomy and steroid replacement model in CD11b-DTR ‘Mac-terminator' mice. These mice are engineered for CD11b promoter-driven expression of the monkey diphtheria toxin (DT) receptor, allowing acute systemic ablation of macrophages by administration of human diphtheria toxin (DT). CD11b-DTR mice were ovariectomised, then 2–4 weeks later were primed with E 2, followed by administration of DT (25 ng/g, ip) to effect macrophage depletion, and BrDU to label proliferating cells. Control mice were given PBS instead of DT. Uterine tissues were stained with F4/80 to detect macrophages, and anti-BrDU to detect BrDU+ epithelial cell nuclei. DT treatment was associated with a depletion of >90% of F4/80+ uterine macrophages. However, the numbers of BrDU+ epithelial cells and the architecture of the luminal epithelial surface and abundance of epithelial glands were similar in control and DT-treated uterine tissues. These data suggest that resident macrophages may not be essential for oestrogen-driven uterine epithelial cell proliferation. In ongoing experiments we are assessing the effect of macrophage depletion on epithelial cell expression of functional markers including those involved in regulation of embryo attachment.

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