Tryptase Activation of Immortalized Human Urothelial Cell Mitogen-Activated Protein Kinase

Marentette, John; Hauser, Paul; Hurst, Robert E.; Klumpp, David J.; Rickard, Alice; McHowat, Jane

doi:10.1371/journal.pone.0069948

Cited by 8 publications

(6 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In general, p38 MAP kinase is associated with inhibition of cell growth, inflammation, and with mediating apoptosis in different cell types. Increases in p38 MAP kinase activity have been demonstrated in IC/BPS immortalized urothelial cells, and increased phosphorylation of p38 MAP kinase has been found in the bladder of IC/BPS patients when compared to controls …”

Section: Discussionmentioning

confidence: 99%

A genome‐scale DNA methylation study in women with interstitial cystitis/bladder pain syndrome

Bradley

Burke

Grenier

et al. 2018

Neurourology and Urodynamics

View full text Add to dashboard Cite

Aims To assess the feasibility of using voided urine samples to perform a DNA methylation study in females with interstitial cystitis/bladder pain syndrome (IC/BPS) as compared to age- and race-matched controls. A unique methylation profile could lead to a non-invasive, reproducible, and objective biomarker that would aid clinicians in the diagnosis of IC/BPS. Methods Nineteen IC/BPS patients and 17 controls were included. IC/BPS patients had an Interstitial Cystitis Symptom Index score of >8; controls had no bladder symptoms. DNA was extracted from pelleted urine sediment. Samples with >500 ng of genomic DNA underwent quantitative DNA methylation assessment using the Illumina Infinium MethylationEPIC BeadChip. Age- and race- matching was applied prior to analysis. Linear regression models were used to compare average methylation between IC/BPS cases and controls at each cytosine guanine dinucleotide site (loci where methylation can occur). Results 16 participants (8 IC/BPS age- and race-matched to 8 controls) had adequate DNA for methylation analysis. The median age was 43.5 years (interquartile range 33.8, 65.0), the median BMI was 27.1 (IQR 22.7, 31.4), and 14 were Caucasian (87.5%). A total of 688,417 CpG sites were analyzed. In exploratory pathway analysis utilizing the top 1000 differentially methylated CpG sites, the mitogen-activated protein kinase (MAPK) pathway was overrepresented by member genes. Conclusions The results demonstrate the feasibility of using voided urine specimens from women with IC/BPS to perform DNA methylation assessments. Additionally, the data suggest genes within or downstream of the MAPK pathway exhibit altered methylation in IC/BPS.

show abstract

Section: Discussionmentioning

confidence: 99%

A genome‐scale DNA methylation study in women with interstitial cystitis/bladder pain syndrome

Bradley

Burke

Grenier

et al. 2018

Neurourology and Urodynamics

View full text Add to dashboard Cite

show abstract

“…Tryptase is the most abundant of the proteases of the MCs granules (Brown et al, ; Cairns and Walls, ). Human tryptase is a potent mitogen (Ruoss et al, ; Brown et al, ; Cairns and Walls, ; Temkin et al, ; McLarty et al, ; Marentette et al, ). Therefore, the role of MCs in the SM stem niche homeostasis should not be ignored.…”

Section: Discussionmentioning

confidence: 99%

Regenerative Potential of Human Schneiderian Membrane: Progenitor Cells and Epithelial‐Mesenchymal Transition

Derjac-Arama

Sarafoleanu

Manea

et al. 2015

The Anatomical Record

View full text Add to dashboard Cite

An innate osteogenic potential of the Schneiderian membrane (SM) is progressively assessed in studies ranging from non-human species to human subjects. It has relevance for endosteal placement and osseointegration. Nestin-expressing osteogenic progenitor cells are allegedly involved in bone formation and remodelling. Nestin phenotype was not assessed previously in human SM. We therefore aimed to fill that particular gap in the literature. Bioptic samples of human adult SM were obtained during surgery from eight adult patients, operated for nonmalignant pathologies. Immunohistochemistry on paraffin-embedded tissue samples used primary antibodies against nestin, CD45, CD146, cytokeratin 7 (CK7), and alpha-smooth muscle actin (a-SMA). Nestin expression was consistently found in endothelial cells, and was scarcely encountered in pericytes, putative stromal stem/progenitor cells, as well as in glandular epithelial cells. Moreover, woven bone formation in the periosteal layer of the SM can also be regarded as evidence of the osteogenic potential of this membrane. Nestin and CD45 expression in cells of the primary bone supports the osteogenic potential of SM nestinexpressing cells and a possible involvement of hematopoietic stem cells in maxillary sinus floor remodeling. CD146, a known inducer of epithelial-mesenchymal transition (EMT), was expressed in epithelia, as was CK7. Isolated stromal cells were found expressing CD146, CK7 and a-SMA, suggesting that regenerative processes happening in the SM may also involve processes of EMT which generate stem/progenitor cells.

show abstract

“…Normal human urothelial cells (HUC) were obtained from ScienCell Research Laboratories (Carlsbad, CA), cell isolations from 3 separate donors were used. Urothelial cells isolated from normal bladder (5 separate donors) and the bladder of patients with IC/PBS (5 separate donors) were immortalized with HPV type 16E6E7as described previously [ 15 , 16 ]. Samples were obtained from IC/PBS patients by biopsy or bladder washing during cystoscopy.…”

Section: Methodsmentioning

confidence: 99%

Impaired Expression of Prostaglandin E2 (PGE2) Synthesis and Degradation Enzymes during Differentiation of Immortalized Urothelial Cells from Patients with Interstitial Cystitis/Painful Bladder Syndrome

2015

Self Cite

View full text Add to dashboard Cite

PurposeThe differentiated superficial cells of the urothelium restrict urine flow into the bladder wall. We have demonstrated that urothelial cells isolated from bladders of patients with interstitial cystitis/painful bladder syndrome (IC/PBS) fail to release PGE2 in response to tryptase. This study examines the expression of PGE2 synthesis and degradation enzymes in urothelial cells during differentiation.Materials and MethodsWe measured immunoprotein expression of cyclooxygenase-2 (COX-2), prostaglandin E2 synthase (PGES) and 15-hydroxyprostaglandin dehydrogenase (PGDH) in human urothelial cells and in immortalized urothelial cells isolated from the bladders of IC/PBS patients or normal subjects during stratification and differentiation produced by increased calcium and fetal bovine serum (Ca/FBS) in the culture medium for 1, 3 and 7 days.ResultsPGES immunoprotein expression increased during differentiation in normal and IC/PBS urothelial cells. COX-2 expression also increased in cells from normal patients following differentiation. Remarkably, no COX-2 expression was detectable in urothelial cells isolated from 3 out of 4 IC/PBS patients. PGDH immunoprotein expression decreased in normal cells after 1 and 3 days of Ca/FBS addition, but returned to normal after 7 days. PGDH expression was unchanged during differentiation at 1 and 3 days, but was more than 2-fold higher at 7 days compared to day 0 in the IC/PBS cells. Urothelial cells isolated from IC/PBS patients demonstrated no PGE2 release in response to tryptase under any of the experimental conditions studied.ConclusionsTaken together, our results indicate that PGE2 release is compromised during stratification and differentiation in IC/PBS urothelium and may contribute to impaired barrier function.

show abstract

Tryptase Activation of Immortalized Human Urothelial Cell Mitogen-Activated Protein Kinase

Cited by 8 publications

References 33 publications

A genome‐scale DNA methylation study in women with interstitial cystitis/bladder pain syndrome

A genome‐scale DNA methylation study in women with interstitial cystitis/bladder pain syndrome

Regenerative Potential of Human Schneiderian Membrane: Progenitor Cells and Epithelial‐Mesenchymal Transition

Impaired Expression of Prostaglandin E2 (PGE2) Synthesis and Degradation Enzymes during Differentiation of Immortalized Urothelial Cells from Patients with Interstitial Cystitis/Painful Bladder Syndrome

Contact Info

Product

Resources

About